Nonfatal Major Adverse Cardiovascular Events Research Articles

Bariatric Metabolic Surgery vs Glucagon-Like Peptide-1 Receptor Agonists and Mortality

ImportanceEvidence regarding the relative effectiveness of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in reducing mortality and major adverse cardiovascular events (MACEs) is limited.ObjectiveTo compare all-cause mortality and nonfatal MACEs associated with BMS vs GLP-1RAs for adults with obesity and diabetes and without known cardiovascular disease.Design, Setting, and ParticipantsThis observational, retrospective cohort study was based on data obtained from the electronic medical records of Clalit Health Services (Clalit), the largest health care organization in Israel. The study included 6070 members aged 24 years or older, who had diabetes and obesity and no prior history of ischemic heart disease, ischemic stroke, or congestive heart failure. Patients who underwent BMS and patients who received GLP-1RAs from January 1, 2008, through December 31, 2021, were matched 1:1 by age, sex, and clinical characteristics. Follow-up ended December 31, 2022.ExposuresInitiation of BMS or GLP-1RAs.Main Outcomes and MeasuresThe primary outcome was all-cause mortality, assessed by multivariate Cox proportional hazards regression models. The secondary outcome was nonfatal MACEs, assessed by multivariate competing risk models.ResultsThe study included 3035 matched pairs of patients (total, 6070; mean [SD] age, 51.0 [9.5] years; 3938 women [64.9%]), who were followed up for a median of 6.8 years (IQR, 4.1-9.4 years). Among those with a diabetes duration of 10 years or less (2371 pairs), mortality was lower for those who underwent BMS than for those treated with GLP-1RAs (hazard ratio [HR], 0.38; 95% CI, 0.25-0.58). This association became nonsignificant when weight loss during the follow-up period was also included in the model (HR, 0.79; 95% CI, 0.43-1.48). Among patients with a duration of diabetes longer than 10 years (664 pairs), no survival advantage was demonstrated for BMS over GLP-1RA (HR, 0.65; 95% CI, 0.39-1.08). The risk for nonfatal MACEs did not differ between the treatment groups (HR, 0.74; 95% CI, 0.49-1.10 among patients with a diabetes duration of ≤10 years; HR, 1.21; 95% CI, 0.80-1.85 among patients with a diabetes duration of >10 years).Conclusions and RelevanceIn this cohort study, BMS was associated with greater reduced mortality compared with first-generation GLP-1RAs among individuals with a diabetes duration of 10 years or less, mediated via greater weight loss. No differences in the risk for mortality were observed between the treatment modalities among individuals with a longer duration of diabetes, nor in the occurrence of nonfatal MACEs among all patients.

Association between Glucose-lowering Treatments and Risk of Diabetic Retinopathy in People with Type 2 Diabetes: A Nationwide Cohort Study.

Glycaemic variability is possibly linked to the development of diabetic retinopathy, and newer second-line glucose-lowering treatments in type 2 diabetes might reduce glycaemic variability. This study aimed to investigate whether newer second-line glucose-lowering treatments are associated with an alternative risk of developing diabetic retinopathy in people with type 2 diabetes. A nationwide cohort of people with type 2 diabetes on second-line glucose-lowering treatment regimens in 2008-2018 was extracted from the Danish National Patient Registry. Adjusted time to diabetic retinopathy was estimated with a Cox Proportional Hazards model. The model was adjusted for age, sex, diabetes duration, alcohol abuse, treatment start year, education, income, history of late-diabetic complications, history of non-fatal major adverse cardiovascular events, history of chronic kidney disease, and history of hypoglycaemic episodes. Treatment regimens of metformin + basal insulin (HR: 3.15, 95% CI: 2.42-4.10) and metformin + glucagon-like peptide-1 receptor agonist (GLP-1-RA, HR: 1.46, 95% CI: 1.09-1.96) were associated with an increased risk of diabetic retinopathy compared with metformin + dipeptidyl peptidase-4 inhibitors (DPP-4i). Treatment with metformin + sodium-glucose cotransporter-2 inhibitor (SGLT2i, HR: 0.77, 95% CI: 0.28-2.11) was associated with the numerically lowest risk of diabetic retinopathy compared with all regimens investigated. Findings from this study indicate that basal insulin and GLP-1-RA are suboptimal second- line choices for people with type 2 diabetes at risk of developing diabetic retinopathy. However, many other considerations concerning the choice of second-line glucose-lowering treatment for type 2 diabetes patients should be taken into account.

Time to benefit of colchicine in patients with cardiovascular disease: A pooled analysis of randomized controlled trials

BackgroundLow-dose colchicine has been shown to lower major adverse cardiovascular events (MACE) among those with cardiovascular disease (CVD). It remains unclear how long a CVD patient needs to live to potentially benefit from colchicine. Our study aimed to determine the time to benefit (TTB) of colchicine in individuals with CVD. MethodsLiterature searches were performed in PubMed for the cardiovascular outcome trial of colchicine in patients with CVD until October 12, 2023. The primary outcome measured was MACE. Reconstructed individual participant data (IPD) and the stratified Cox proportional hazards model were used to calculate the hazard ratio (HR) and 95 % confidence interval (CI) to estimate the efficacy of colchicine, and Weibull survival curves were fitted to estimate TTB for specific absolute risk reduction (ARR) thresholds (0.002, 0.005, and 0.01). ResultsFour trials randomizing 11,594 adults aged between 59.8 and 66.5 years were included (follow-up duration: 12–28.6 months). Compared with placebo, colchicine reduced the risk of MACE (HR 0.68, 95 % CI: 0.60 to 0.78) but had no impact on cardiovascular and all-cause mortality. A TTB of 11.0 months (95 % CI: 0.59 to 21.3) was estimated to be needed to prevent 1 MACE in 100-colchicine-treated patients. The TTB for acute coronary syndrome was similar compared to stable coronary artery disease (10.7 vs. 11.2 months for ARR = 0.010). ConclusionsBy using reconstructed IPD, this pooled analysis demonstrated that colchicine was associated with reduced nonfatal MACE, and the TTB was approximately 11.0 months to prevent 1 MACE per 100 patients.

(294) Revisiting Risk of Testosterone Therapy: Assessing the Impact of Supratherapeutic Levels on MACE and Mortality

Abstract Introduction The benefits and risks of testosterone therapy (TT) have been a subject of long-standing debate. The recent TRAVERSE trial demonstrated that men who received TT did not show an increased risk of major adverse cardiovascular events (MACE) or mortality. However, it is essential to note that the median post-treatment testosterone levels were found to be less than 400ng/dL. Therefore, our investigation aims to assess whether supra-therapeutic T levels (>1000ng/dL) are associated with an elevated risk of MACE and/or mortality. Objective To use data from the National Health and Nutrition Examination Survey (NHANES) 2011-2016 to determine whether supratherapeutic testosterone levels (> 1000 ng/dL) are associated with higher rates of all-cause mortality or MACE. Additionally, to determine whether there was a higher rate of MACE among patients who died. Methods We collected data from the NHANES 2011-2016 Continuous Files and linked them to the National Death Index (NDI) through 2019. The NHANES is a national survey run by the Center for Disease Control that assesses the health status of United States residents by sampling of populations across the country. The survey collects socio-demographic data, lab values, dietary health, clinical variables and body measurements. NDI is a centralized database of United States death record information on file in state vital statistics offices. We included male participants aged 18 years and older with data on total testosterone and who were eligible for mortality data. We compared participants with testosterone > 1000 ng/dL against those with <1000 ng/dL, with the assumption that those > 1000 ng/dL had supratherapeutic levels of testosterone from testosterone therapy. Our primary outcome was mortality, with secondary outcomes of mortality due to MACE. We additionally analyzed association with MACE as the primary cause of mortality among participants who had died. MACE was determined by those who were categorized as dying of “diseases of the heart” or “cerebrovascular diseases.” We used binary logistic regression and controlled for age, race, body mass index, and history of myocardial infarction. Statistical significance was assessed at p<0.05. All analyses were performed on STATA MP 17. Results We identified 7,790 males aged 18 or older with mortality data. Of those, 7,715 had testosterone <1000 and 75 men had testosterone > 1000. Among all patients in our cohort, 643 died of all causes, and 199 died of MACE. In the multivariable logistic regression adjusted for potentially confounding variables, we found testosterone >1000 was associated with all-cause mortality (OR 2.59, 95% CI 1.29-5.20, p=0.007). There was no association with mortality from MACE in either all participants (OR 0.60, 95% CI 0.08-4.45, p=0.615) or among those who died (OR 0.28, 95% CI 0.03-2.17, p=0.221). Conclusions Supratherapeutic levels of testosterone are associated with all-cause mortality by 2019 in NHANES participants from 2011-2016. There were no associations with MACE in this population, although overall numbers of death from MACE were low in this data set. Future studies should examine longitudinal data across a greater duration and consider non-fatal MACE events in men who achieve supra-therapeutic levels on TT. Disclosure No.

Adherence to guideline-directed medical therapy and 3-year clinical outcome following acute myocardial infarction

Abstract Aims Despite the well-established clinical benefits and strong recommendations in clinical guidelines, adherence to guideline-directed medical therapy (GDMT) is known to be insufficient. We investigated the adherence to GDMT and its impact on the 3-year clinical outcomes in patients with acute myocardial infarction (AMI). Methods and results Source data were obtained from KAMIR-NIH, a Korean multicenter observational registry. GDMT was defined according to the ACC/AHA class I recommendations. Adherence to GDMT was assessed at discharge and every year thereafter. The differences in clinical characteristics between patients receiving and those not receiving GDMT were adjusted using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary endpoint was major adverse cardiovascular events (MACE), which was a composite of all-cause death and non-fatal MACE, including MI, revascularization, or stroke. Of 12,815 patients, GDMT adherence was 70.2% at discharge, and decreased gradually into 54.6% at 3-year. GDMT at discharge was associated with lower MACE risk in the unadjusted analysis (HR=0.51, 95%CI=0.47–0.55, p<0.001) and also in the PSM- or IPTW-adjusted analyses (HR=0.77, 95%CI=0.69–0.86; HR=0.79, 95%CI=0.72–0.86; p<0.001, all). These findings were replicated in the 1-year or 2-year landmark analyses (HR=0.58 to 0.82, p<0.01, all). Conclusion Adherence to GDMT was suboptimal among patients with AMI in Korea. As the adherence to GDMT was associated with a lower incidence of MACE during 3-year follow-up, the maintenance of long-term GDMT might be crucial for patients with AMI.Structured Graphical Abstract

Association of mineral and bone biomarkers with adverse cardiovascular outcomes and mortality in the German Chronic Kidney Disease (GCKD) cohort

Mineral and bone disorder (MBD) in chronic kidney disease (CKD) is tightly linked to cardiovascular disease (CVD). In this study, we aimed to compare the prognostic value of nine MBD biomarkers to determine those associated best with adverse cardiovascular (CV) outcomes and mortality. In 5 217 participants of the German CKD (GCKD) study enrolled with an estimated glomerular filtration rate (eGFR) between 30–60 mL·min−1 per 1.73 m2 or overt proteinuria, serum osteoprotegerin (OPG), C-terminal fibroblast growth factor-23 (FGF23), intact parathyroid hormone (iPTH), bone alkaline phosphatase (BAP), cross-linked C-telopeptide of type 1 collagen (CTX1), procollagen 1 intact N-terminal propeptide (P1NP), phosphate, calcium, and 25-OH vitamin D were measured at baseline. Participants with missing values among these parameters (n = 971) were excluded, leaving a total of 4 246 participants for analysis. During a median follow-up of 6.5 years, 387 non-CV deaths, 173 CV deaths, 645 nonfatal major adverse CV events (MACEs) and 368 hospitalizations for congestive heart failure (CHF) were observed. OPG and FGF23 were associated with all outcomes, with the highest hazard ratios (HRs) for OPG. In the final Cox regression model, adjusted for CV risk factors, including kidney function and all other investigated biomarkers, each standard deviation increase in OPG was associated with non-CV death (HR 1.76, 95% CI: 1.35–2.30), CV death (HR 2.18, 95% CI: 1.50–3.16), MACE (HR 1.38, 95% CI: 1.12–1.71) and hospitalization for CHF (HR 2.05, 95% CI: 1.56–2.69). Out of the nine biomarkers examined, stratification based on serum OPG best identified the CKD patients who were at the highest risk for any adverse CV outcome and mortality.

The risk of major adverse cardiovascular events associated with the use of hypnotics in patients with insomnia

ObjectivesTo examine whether hypnotic use in patients with insomnia reduces major adverse cardiovascular events, including all-cause mortality and nonfatal major adverse cardiovascular events. MethodsUsing the Veterans Affairs Corporate Data Warehouse, we conducted a retrospective cohort study of 16,064 patients who were newly diagnosed with insomnia between January 1, 2010, and December 31, 2019. A pair of 3912 hypnotic users and nonusers were selected based on a 1:1 propensity score methodology. The primary outcome was extended major adverse cardiovascular events, a composite of the first occurrence of all-cause mortality or nonfatal major adverse cardiovascular events. ResultsDuring the median follow-up of 4.8 years, a total of 2791 composite events occurred, including 2033 deaths and 762 nonfatal major adverse cardiovascular events. Although the incidence rates of major adverse cardiovascular events were comparable between hypnotic users and nonusers in the propensity-matched cohort, users of benzodiazepines and Z-drugs had a higher risk of all-cause mortality (hazard ratio 1.47 [95% CI, 1.17-1.88] and 1.20 [95% CI, 1.03-1.39], respectively), while serotonin antagonist and reuptake inhibitors users had a survival advantage (hazard ratio 0.79 [95% CI, 0.69-0.91]) compared with nonusers. There were no differences in the risk of nonfatal major adverse cardiovascular events between all classes of hypnotics. Male patients and those aged 60 years or younger who were using benzodiazepines or Z-drugs experienced higher major adverse cardiovascular events than their counterparts. ConclusionsIn patients with newly diagnosed insomnia, treatment with hypnotics resulted in higher extended major adverse cardiovascular events but not nonfatal major adverse cardiovascular events with benzodiazepine and Z-drug users compared with nonusers. The use of serotonin antagonist and reuptake inhibitors agents had a protective effect against major adverse cardiovascular events warranting further investigation.

The association of intensive blood pressure treatment and non-fatal cardiovascular or serious adverse events in older adults with mortality: mediation analysis in SPRINT.

Randomized clinical trials of hypertension treatment intensity evaluate the effects on incident major adverse cardiovascular events (MACEs) and serious adverse events (SAEs). Occurrences after a non-fatal index event have not been rigorously evaluated. The aim of this study was to evaluate the association of intensive (<120 mmHg) to standard (<140 mmHg) blood pressure (BP) treatment with mortality mediated through a non-fatal MACE or non-fatal SAE in 9361 participants in the Systolic Blood Pressure Intervention Trial. Logistic regression and causal mediation modelling to obtain direct and mediated effects of intensive BP treatment. Primary outcome was all-cause mortality (ACM). Secondary outcomes were cardiovascular (CVM) and non-CV mortality (non-CVM). The direct effect of intensive treatment was a lowering of ACM [odds ratio (OR) 0.75, 95% confidence interval (CI): 0.60-0.94]. The MACE-mediated effect substantially attenuated (OR 0.96, 95% CI: 0.92-0.99) ACM, while the SAE-mediated effect was associated with increased (OR 1.03, 95% CI: 1.01-1.05) ACM. Similar patterns were noted for intensive BP treatment on CVM and non-CVM. We also noted that SAE incidence was 3.9-fold higher than MACE incidence (13.7 vs. 3.5%), and there were a total of 365 (3.9%) ACM cases, with non-CVM being 2.6-fold higher than CVM [2.81% (263/9361) vs. 1.09% (102/9361)]. The SAE to MACE and non-CVM to CVM preponderance was found across all age groups, with the ≥80-year age group having the highest differences. The current analytic techniques demonstrated that intensive BP treatment was associated with an attenuated mortality benefit when it was MACE-mediated and possibly harmful when it was SAE-mediated. Current cardiovascular trial reporting of treatment effects does not allow expansion of the lens to focus on important occurrences after the index event.

Adherence to guideline-directed medical therapy and 3-year clinical outcome following acute myocardial infarction.

Despite the well-established clinical benefits and strong recommendations in clinical guidelines, adherence to guideline-directed medical therapy (GDMT) is known to be insufficient. We investigated the adherence to GDMT and its impact on the 3-year clinical outcomes in patients with acute myocardial infarction (AMI). Source data were obtained from KAMIR-NIH, a Korean multi-centre observational registry. GDMT was defined according to the ACC/AHA Class I recommendations. Adherence to GDMT was assessed at discharge and every year thereafter. The differences in clinical characteristics between patients receiving and those not receiving GDMT were adjusted using propensity score matching (PSM) or inverse probability of treatment weighting (IPTW). The primary endpoint was major adverse cardiovascular events (MACE), which was a composite of all-cause death and non-fatal MACE, including myocardial infarction (MI), revascularization, or stroke. Of 12 815 patients, GDMT adherence was 70.2% at discharge, and decreased gradually into 54.6% at 3-year. GDMT at discharge was associated with lower MACE risk in the unadjusted analysis [hazard ratio (HR) = 0.51, 95% confidence intervals (CI) = 0.47-0.55, P < 0.001] and also in the PSM- or IPTW-adjusted analyses (HR = 0.77, 95% CI = 0.69-0.86; HR = 0.79, 95% CI = 0.72-0.86; P < 0.001, all). These findings were replicated in the 1-year or 2-year landmark analyses (HR = 0.58 to 0.82, P < 0.01, all). Adherence to GDMT was sub-optimal among patients with AMI in Korea. As the adherence to GDMT was associated with a lower incidence of MACE during 3-year follow-up, the maintenance of long-term GDMT might be crucial for patients with AMI.

Blood Type A1 Mismatch Does Not Affect Heart Transplant Outcomes at One Year.

There are subtypes within blood type A, termed non-A1, that have reduced expression of A antigen on cell surfaces. This can result in the development of anti-A1 antibodies. There is limited information regarding the impact of this in heart transplant (HTx) recipients. We conducted a single-center cohort study of 142 Type A HTx recipients in which we compared outcomes of a match group (an A1/O heart into an A1 recipient or a non-A1/O heart into a non-A1 recipient) with a mismatch group (an A1 heart into a non-A1 recipient or a non-A1 heart into an A1 recipient). At one year post-transplant, there were no differences between the groups in survival, freedom from non-fatal major adverse cardiovascular events, freedom from any treated rejection, or freedom from cardiac allograft vasculopathy. There was an increased hospital length of stay in the mismatch group (13.5 vs. 17.1 days, p = 0.04). Our study showed that A1 mismatch was not associated with worse outcomes at one year post-HTx.

Effect of metabolic control on recurrent major adverse cardiovascular events and cardiovascular mortality in patients with premature coronary artery disease: Results of the Genetics of Atherosclerotic Disease study

Background and aimsCoronary artery disease (CAD) is the leading cause of death around the world, and its rate of presentation is increasing at young ages. Despite the evidence that secondary prevention in CAD reduces the risk of recurrent major adverse cardiovascular events (MACE), no studies have analyzed the composite control of blood pressure, lipids, and glucose control in premature CAD. Methods and resultsThis was a real-world prospective cohort study of patients with premature CAD. The composite control in blood pressure <140/80 mmHg, LDL-C <70 mg/dL, non-HDL-C <100 mg/dL, and Hemoglobin A1c <8% was considered as metabolic control. The primary endpoint was the occurrence of non-fatal and fatal MACE. The data included 1042 patients with premature CAD. The mean age of the patients was 54.1 ± 8.1 years, 18.5% were women, and had a median follow-up of 59.1 ± 11.8 months. Of them, 7% had non-fatal MACE, and 4% had a fatal MACE. Overall, 21.3% achieved metabolic control, and 3.0% did not achieve any target. Cox regression analysis showed that percutaneous coronary intervention (Hazzard ratio = 1.883 [95% CI, 1.131–3.136]), C-reactive protein (1.046 [1.020–1.073]), blood pressure >140/90 mmHg (2.686 [1.506–4.791]), fibrates (2.032 [1.160–3.562]), calcium channel blockers (2.082 [1.158–3.744]) had greater risk to present a recurrent non-fatal MACE; whereas familial history of premature CAD (2.419 [1.240–4.721]), heart failure (2.139 [1.032–4.433]), LDL-C >70 mg/dL (4.594 [1.401–15.069]), and diuretics (3.328 [1.677–6.605]) were associated with cardiovascular mortality. ConclusionsThe composite goal achievement in lipids, blood pressure and glucose, reduced the risk for recurrent MACE in 80%.

Usefulness of Statins as Secondary Prevention Against Recurrent and Terminal Major Adverse Cardiovascular Events

Clinical guidelines recommend statins for patients with atherosclerotic cardiovascular disease (ASCVD), but many remain untreated. The goal of this study was to assess the impact of statin use on recurrent major adverse cardiovascular events (MACE). This study used medical records and insurance claims from 4 health care systems in the United States. Eligible adults who survived an ASCVD hospitalization from September 2013 to September 2014 were followed for 1 year. A multivariable extended Cox model examined the outcome of time-to-first MACE, then a multivariable joint marginal model investigated the association between post-index statin use and nonfatal and fatal MACE. There were 8,168 subjects in this study; 3,866 filled a statin prescription ≤90 days before the index ASCVD event (47.33%) and 4,152 filled a statin prescription after the index ASCVD event (50.83%). These post-index statin users were younger, with more co-morbidities. There were 763 events (315/763, 41.3% terminal) experienced by 686 (8.4%) patients. The adjusted overall MACE risk reduction was 18% (HR 0.82, 95% CI 0.70 to 0.95, p=0.007) and was more substantial in the first 180 days (HR 0.72, 95% CI 0.60 to 0.86, p <0.001). There was a nonsignificant 19% reduction in the number of nonfatal MACE (rate ratio 0.81, 95% CI 0.49 to 1.32, p=0.394) and a 65% reduction in the risk of all-cause death (HR 0.35, 95% CI 0.22 to 0.56, p <0.001). In conclusion, we found a modest increase in statin use after an ASCVD event, with nearly half of the patients untreated. The primary benefit of statin use was protection against early death. Statin use had the greatest impact in the first 6 months after an ASCVD event; therefore, it is crucial for patients to quickly adhere to this therapy.

Left atrial strain is associated with adverse cardiovascular events in patients with end-stage renal disease: Findings from the Cardiac, Endothelial Function and Arterial Stiffness in ESRD (CERES) study.

IntroductionWe lack cardiovascular (CV) markers for patients with end‐stage renal disease (ESRD), and left atrial (LA) strain has not been studied definitively in this population. We examined associations of LA reservoir, conduit, and booster strain with major adverse cardiovascular events (MACE) among stable patients with ESRD on dialysis.MethodsOne hundred and ninety patients in the Cardiac, Endothelial and Arterial Stiffness in ESRD study underwent echocardiography, including strain imaging. The primary outcome was 2‐year composite non‐fatal MACE or CV death. We performed Cox proportional hazards regression for LA strain measures, adjusting for demographics, comorbidities, left ventricular global longitudinal strain (LV GLS), E/e′ and LA volume index.FindingsMean ± SD LA reservoir strain was 24.1 ± 7.0%, and LA conduit strain 11.9 ± 5.1%. In age‐adjusted analyses, lower LA reservoir strain and LA conduit strain were associated with the primary outcome (HR per 1‐SD worsening LA strain parameter = 1.57 [95% CI 1.2–2.1], p = 0.003 and 1.68 [95% CI 1.2–2.3], p = 0.002, respectively). After adjusting for comorbidities, LA reservoir strain remained associated with the primary outcome and with deaths alone, and LA conduit strain with the primary outcome and hospitalizations alone (p < 0.05 for all). Associations of LA conduit strain were independent of LV GLS. Associations were stronger in participants with serum albumin <3.6 mg/dl (p for interaction 0.008).DiscussionLeft atrial reservoir strain and conduit strain were independently associated with MACE among patients with ESRD. Our study provides unique ascertainment of CV hospitalizations not attributed to missed dialysis, and LA conduit strain was a strong marker for this outcome.

Severe Periodontal Disease Increases Acute Myocardial Infarction and Stroke: A 10-Year Retrospective Follow-up Study

This study aimed to evaluate the causal association of periodontal disease with acute myocardial infarction (AMI) and stroke, after controlling for various confounders among the Korean population. A retrospective cohort study using the National Health Insurance Service–National Health Screening Cohort (NHIS-HEALS) was performed during 2002 to 2015 (baseline: 2002 to 2005; follow-up: 2006 to 2015) in the Republic of Korea. A total of 298,128 participants with no history of AMI or stroke were followed up for 10 y. AMI and stroke were defined by a diagnosis using the International Classification of Diseases, 10th Revision (ICD-10) guideline. Periodontal condition was classified into 3 groups (healthy, moderate periodontal disease, severe periodontal disease [SPD]) using the combination of ICD codes, treatment codes in the NHIS, and recommendation of periodontal treatment by the dentists in HEALS. Various confounders, such as sociodemographic, behavioral, systemic, and oral health factors, including hypercholesterolemia, were considered. Multivariable Cox regression analysis was applied to estimate adjusted incidence rate ratio (adjusted hazard ratio [aHR]) based on person-year of periodontal condition for AMI, stroke, and nonfatal major adverse cardiovascular events (MACEs) encompassing AMI or stroke controlling for various confounders. Stratified analyses according to age group, sex, and toothbrushing frequency were also performed. After controlling for various confounders, participants with SPD compared with non-SPD participants had a higher incidence by 11% for AMI (aHR, 1.11; 95% confidence interval [CI], 1.02–1.20), by 3.5% for stroke (aHR, 1.035; 95% CI, 1.01–1.07), and by 4.1% for MACEs (aHR, 1.04; 95% CI, 1.01–1.07). The association of SPD with AMI and MACE was highly modified in females and adults aged 40 to 59 y. In the total Korean population, SPD increased total AMI events by 4.3%, total stroke events by 1.4%, and the total MACEs by 1.6%. Our data confirmed that SPD was causally associated with the new events of AMI and stroke.

Added value of high-risk plaque criteria by coronary CTA for prediction of long-term outcomes

Background and aimsLong-term data relating coronary computed tomography angiography (CTA) to coronary artery disease (CAD) prognosis including novel CTA-biomarkers (“high–risk plaque criteria”) is scarce. The aim of this study was to define predictors of long-term outcomes. Methods1430 low-to-intermediate risk patients (57.9 ± 11.1 years; 44.4% females) who underwent CTA and coronary calcium scoring (CCS) were prospectively enrolled. CTAs were evaluated for (1) stenosis severity CADRADS 0–4 (minimal <25%, mild 25–50%, moderate 50–70%, severe >70%), (2) mixed plaque burden weighted for non-calcified plaque (NCP), and (3) high-risk-plaque (HRP) criteria: low-attenuation-plaque (LAP), napkin-ring-sign, spotty calcifications <3 mm or remodeling index >1.1. Endpoints were all-cause and cardiovascular mortality, composite fatal and nonfatal major adverse cardiovascular events (MACE). ResultsOver a mean follow-up of 10.55 years ± 1.98, 106 patients (7.4%) died, 25 from cardiovascular events (1.75%). Composite MACE occurred in 57 (3.9%) patients. In patients with negative CTA, cardiovascular mortality and MACE rates were 0% and 0.2%.Stenosis severity by CTA predicted all 3 endpoints (p < 0.001) while CCS >100 AU predicted only all-cause mortality (p = 0.045) but not MACE.The high risk plaque criteria LAP <60HU (HR: 4.00, 95%CI 95% 1.52–10.52, p = 0.005) and napkin-ring (HR 4.11, CI 95% 1.77–9.52, p = 0.001) predicted MACE but not all-cause-mortality, after adjusting for risk factors, while spotty calcification and remodeling index did not. Similarly, mixed plaque burden predicted MACE (p < 0.0001).HRP criteria, if added to CADRADS + CCS for prediction of MACE, were superior to CCS (c = 0.816 vs 0.716, p < 0.001). In 33.5% of CCS zero patients, non-calcified fibroatheroma were found. ConclusionsLong-term prognosis is excellent if CTA is negative for CAD. The high-risk plaque criteria LAP<60HU and napkin-ring-sign were independent predictors of MACE while HRP criteria added incremental prognostic value.

Major Adverse Cardiovascular Events after Treatment in Early-stage Breast Cancer Patients Receiving Hormone Therapy

This nationwide population-based study investigated the differences in the risks of major adverse cardiovascular events (MACEs) among patients with hormone receptor–positive early-stage breast cancer undergoing different combinations of adjuvant treatments in Taiwan. Data from the National Health Insurance Research Database (NHIRD) and Taiwan Cancer Registry (TCR) along with the national mortality data were used. Patients who underwent surgery as the first mode of treatment were divided into four groups based on the subsequent adjuvant therapy received: hormone therapy (H), hormone therapy + chemotherapy (CH), hormone therapy + radiotherapy (RH), and hormone therapy + radiotherapy + chemotherapy (CRH) groups. The risks of fatal and nonfatal MACE among the groups were examined using the inverse probability of treatment weighted hazard ratio (IPTW-HR). Adjuvant treatment, age, tumour size, and comorbidities significantly affected the risks of MACEs among the 19,007 patients analysed. For nonfatal MACEs, the IPTW-HR was significantly lower in the CH group compare to the H group (0.704, 95% confidence interval [CI]: 0.516–0.961). No significant differences in the risks for fatal MACE were observed among the four groups. The IPTW-HRs for haemorrhagic stroke in the CH group was 0.424 (95% CI: 0.188–0.957), for congestive heart failure (CHF) in the RH group was 0.260 (95% CI: 0.088–0.762), and for ischaemic heart disease in the CRH group was 0.544 (95% CI: 0.317–0.934). Increase in the adjuvant modality does not necessarily increase the nonfatal or fatal MACE risks. Cardiac health should be monitored even in patients receiving hormone therapy alone.

P5674Direct comparison of three high-sensitivity cardiac troponins in syncope

Abstract Background It is unknown, whether high-sensitivity cardiac troponin I (hs-cTnI) or hs-cTnT provide higher accuracy for the diagnosis and risk-stratification of patients with syncope. Methods We directly compared the diagnostic and prognostic accuracy of hs-cTnI and hs-cTnT in a prospective international multicenter study enrolling patients older than 40 years presenting with syncope to the emergency department (ED). Hs-cTnI/T concentrations were measured in a blinded fashion using three assays. Cardiac syncope, as adjudicated by two independent physicians using all available clinical information including 1-year follow-up, was the diagnostic endpoint. Death and nonfatal major adverse cardiovascular events (MACE) at 5, 30 and 720 days were the prognostic endpoints. Results Among 1219 patients, cardiac syncope was the adjudicated final diagnosis in 204 (16.7%). All three hs-cTn showed higher concentrations in patients with cardiac syncope compared with other causes (all p&lt;0.01, Figure 1) and remained independent predictors of cardiac syncope in multivariable models. While the diagnostic accuracy of the three assays for cardiac syncope was similar (area under the curve (AUC) of 0.76–0.77 (95% CI, 0.72–0.80, p&gt;0.05 for all direct comparisons)), the percentage of patients above/below the assay-specific cut-off strongly varied (Figure 1). The prognostic accuracy of hs-cTnI/T was comparable among the assays and very high for imminent (within 5 days) death (AUC 0.93–0.94), and high for 30 and 720-day death (AUC 0.74–0.8), as well as MACE (AUC 0.74–0.78). Figure 1 Conclusion Hs-cTnI/T concentrations may have clinical utility in patients presenting with syncope as they provide diagnostic as well as prognostic information. Acknowledgement/Funding Swiss National Science Foundation, Swiss Heart Foundation, Cardiovascular Research Foundation, Basel (Switzerland), University Basel (Switzerland)

Major Adverse Cardiovascular Events Following Simultaneous Pancreas and Kidney Transplantation in the United Kingdom.

People with type 1 diabetes and kidney failure have an increased risk for major adverse cardiovascular events (MACE). Simultaneous pancreas and kidney transplantation (SPKT) improves survival, but the long-term risk for MACE is uncertain. We assessed the frequency and risk factors for MACE (defined as fatal cardiovascular disease and nonfatal myocardial infarction or stroke) and related nonfatal MACE to allograft failure in SPKT recipients with type 1 diabetes who underwent transplantation between 2001 and 2015 in the U.K. In a subgroup, we related a pretransplant cardiovascular risk score to MACE. During 5 years of follow-up, 133 of 1,699 SPKT recipients (7.8%) experienced a MACE. In covariate-adjusted models, age (hazard ratio 1.04 per year [95% CI 1.01-1.07]), prior myocardial infarction (2.6 [1.3-5.0]), stroke (2.3 [1.2-4.7]), amputation (2.0 [1.02-3.7]), donor history of hypertension (1.8 [1.05-3.2]), and waiting time (1.02 per month [1.0-1.04]) were significant predictors. Nonfatal MACE predicted subsequent allograft failure (renal 1.6 [1.06-2.6]; pancreas 1.7 [1.09-2.6]). In the subgroup, the pretransplant cardiovascular risk score predicted MACE (1.04 per 1% increment [1.02-1.06]). We report a high rate of MACE in SPKT recipients. There are a number of variables that predict MACE, while nonfatal MACE increase the risk of subsequent allograft failure. It may be beneficial that organs from hypertensive donors are matched to recipients with lower cardiovascular risk. Pretransplant cardiovascular risk scoring may help to identify patients who would benefit from risk factor optimization or alternative transplant therapies and warrants validation nationally.

Cardiovascular Efficacy and Safety of PCSK9 Inhibitors: Systematic Review and Meta-analysis Including the ODYSSEY OUTCOMES Trial

Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors are efficacious lipid-lowering agents, but more precise estimates of their effects on major adverse cardiovascular events (MACE), mortality, and safety are needed. We systematically reviewed and meta-analyzed randomized controlled trials with durations ≥ 6 months comparing MACE, mortality, and safety with PCSK9 inhibitors vs control. We searched CENTRAL, Embase, MedLine and the grey literature to November 7, 2018. From 2048 articles, we included 23 trials (n = 60,723). PCSK9 inhibitors reduced MACE (relative risk, 0.83; 95% confidence interval, 0.78-0.88), but did not clearly reduce mortality (relative risk, 0.93; 95% confidence interval, 0.85-1.02) or increase adverse events. In conclusion, PCSK9 inhibitors reduce nonfatal MACE, are well tolerated, but effects on mortality remain unclear.

The effect of radial pulse spectrum on the risk of major adverse cardiovascular events in patients with type 2 diabetes

Radial pulse spectrum has been shown to correlate with coronary stenosis in patients with type 2 diabetes mellitus (T2DM). In academia, it has not been demonstrated that the radial artery pulse spectrum is an independent risk factor for major adverse cardiovascular events (MACE), including myocardial infarction, stroke, and all-cause mortality. The primary objective of this study is to assess the risk of MACE, in patients with T2DM and to determine if an increase in MACE would be associated with a first harmonic (C1) increase in the radial artery pulse. 1972 consecutive patients with T2DM were enrolled. All subjects received measurements of radial pulse waves at baseline. Harmonic analysis of radial pressure wave was performed. The hazard ratios for MACE and its 95% confident interval were estimated using Cox proportional hazard model. The follow-up period lasted for one year. MACE was detected in 232 (11.8%) of those with T2DM. The log-rank test demonstrated that the cumulative incidence of patients with C1 above 0.96 was greater than those with C1 bellow 0.96. Comparing the patients with C1 smaller than first quartile to the patients with C1 greater than third quartile, higher C1 increased the cardiovascular risks as follows: MACE (Hazard ratio,1.93; 95% CI,1.31–2.86), stroke (Hazard ratio, 1.61; 95% CI, 0.90–2.90), myocardial infarction (Hazard ratio, 2.23; 95% CI, 1.33–3.74). The risk for the composite MACE increased continuously as C1 increased (P < 0.001 for trend). The hazard ratio and trend for all-cause mortality were not significant. Increased C1 resulted in increased risk for nonfatal stroke, and nonfatal myocardial infarction among patients with T2DM. Our results indicate that the degree of C1 is a risk factor for nonfatal MACE. Therefore, the radial pulse spectrum could identify patients with T2DM at high risk of nonfatal MACE.