Conventional Risk Factors Research Articles

Sex differences in cardiac troponin trajectories over the life course

Abstract Background Cardiac troponin is a promising biomarker that may improve cardiovascular risk prediction. Previously, important differences have been demonstrated between cardiac troponin concentration in women and men. At this point, it is unknown whether changes in cardiac troponin concentration over the life course differ in women and men and whether this impacts cardiovascular risk prediction. Purpose Insights into sex-specific cardiac troponin trajectories and how these are influenced by risk factors are necessary to ensure approaches to the prevention of cardiovascular disease in women and men are equitable. Therefore, we examined whether age- and risk factor-related changes in cardiac troponin over the life course differ by sex and if the trajectory of cardiac troponin was informative in respect of cardiovascular outcomes in women and men in the general population. Methods In the Whitehall II cohort, high-sensitivity cardiac troponin I concentrations were measured on three occasions over a 15-year period. Using linear mixed-effects models, the sex-specific trajectories of cardiac troponin were evaluated, and the relationship with conventional cardiovascular risk factors determined. Using multistate joint models, the association between sex-specific trajectories of cardiac troponin and a composite outcome of non-fatal myocardial infarction, non-fatal stroke, or cardiovascular death was evaluated. Results In 2,142 women and 5,151 men (mean 58±7 and 57±7 years, respectively) there were 177 (8.3%) and 520 (10.1%) outcome events, respectively, during a median follow-up of 20.9 [25th to 75th percentile, 15.8 to 21.3] years. Cardiac troponin concentrations were persistently lower in women than in men (median baseline concentration: 2.4 [25th to 75th percentile, 1.7 to 3.6] ng/L versus 3.7 [25th to 75th percentile, 2.6 to 5.8] ng/L, respectively, P<0.001, Figure 1A), with women exhibiting a relatively larger increase with advancing age as compared with men (Pinteraction<0.001, Figure 1B). Apart from age, a significant and divergent interaction with sex was found for the association between cardiac troponin and body mass index (Pinteraction=0.008) and diabetes (Pinteraction=0.003). During follow-up, cardiac troponin concentrations were associated to the outcome in both women and men (adjusted HR per two-fold difference [95% CI], 1.34 [1.17-1.52] and 1.30 [1.21-1.40], respectively, Pinteraction=0.752). The slope of cardiac troponin was significantly associated with the outcome in women, but not in men (adjusted HR [95% CI], 2.70 [1.01-7.33] and 1.31 [0.62-2.75], respectively, Pinteraction=0.250). Conclusion Trajectories of cardiac troponin differ between women and men in the general population, with differing associations to conventional risk factors and cardiovascular outcomes. Our findings highlight the importance of a sex-specific approach when serial cardiac troponin testing is applied for cardiovascular risk prediction.

Impact of coronary artery calcium on the prognosis of heterozygous familial hypercholesterolemia

Abstract Aims This study was designed to examine the association between coronary artery calcium (CAC) and major adverse cardiac events (MACEs) and to estimate CAC progression in patients with familial hypercholesterolemia (FH) in primary prevention settings. Methods and results Data of patients with FH admitted to our university hospital between 2000 and 2020, who underwent CAC measurement and were followed up (N = 622, male = 306), were retrospectively reviewed. Risk factors for MACEs were determined using the Cox proportional hazard model. The median follow-up duration was 13.2 years (interquartile range: 9.8–18.4 years). We observed 132 MACEs during the follow-up period. The event rate per 1,000 person-years for CAC scores of 0 (N = 283 [45.5%]), 1–100 (N = 260 [41.8%]), and >100 (N = 79 [12.7%]) was 1.2, 17.0, and 78.8, respectively. Log (CAC score+1) was a significant predictor of the occurrence of MACEs (hazard ratio: 3.24; 95% confidence interval: 1.68–4.80; p = 5.6×10−5) in the multivariate Cox regression analysis, independent of other factors. The risk discrimination of MACEs was enhanced by adding CAC information to other conventional risk factors (C-statistics: 0.833–0.934; p = 1.4×10−15). The regression equations between age and the CAC score in male and female were Y = 0.074X–1.52 and Y = 0. 087X–3.21, respectively. Conclusion CAC score helps in further risk stratification in patients with FH. Furthermore, the average age of CAC onset was 21 years in male and 37 years in females.

A better understanding of coronary artery disease molecular biology through an intermediate phenotype

Abstract Coronary Artery Disease (CAD) remains a common cause of death worldwide; over half of these deaths are asymptomatic until the first fatal presentation. Previous studies have often compared coronary artery calcification (CAC) with coronary stenosis or its sequelae. However, the genetic contribution to CAC in sub-clinical atherosclerosis is controversial. Purpose This study intended to assess the relationship between a set of single nucleotide polymorphisms associated with CAD (GWAS) and CAC score in an asymptomatic population. Methods Prospective study performed in an asymptomatic cohort from GENEMACOR population-based sample of 1207 subjects aged 51.7±8.3, 73.8 male, without apparent prior CAD. CAC score was performed by cardiac computed tomography and reported as Agatston units according to the Hoff nomogram (Low, Moderate and High-risk categories). For the present work, we considered two groups: Group 1 (0≤CAC<100 and Percentile<50) and Group 2 (CAC≥100 or Percentile≥50). We genotyped thirty-three single nucleotide polymorphisms (SNP) associated with CAD by TaqMan real-time PCR. Anthropometric, conventional, and biochemical risk factors were assessed. The association of these SNPs with CAC score groups were evaluated by bivariate and multivariate logistic regression analysis, and the dominant genetic model was considered for comparison. Results After bivariate analysis, only PHACTR1 rs1332844 C>T (CT+TT genetic model) showed a significative association with CAC score (OR=1.45; 95%CI 1.09-1.94; p=0.011). Multivariate logistic regression analysis, adjusted to traditional risk factors, genetic model and CAC score showed that PHACTR1 rs1332844 remained in the equation as significantly associated to CAC score (P=0.009) together with age (0.0001), hypertension (0.006), Diabetes (0.0001), smoking (0.001) and obesity (0.028). Conclusion PHACTR1 genetic variant is known to contribute to atherosclerosis and plaque formation. In the present study it showed a significant association with plaque calcium. More research in this field is critical to understanding the genetic basis of CAD through an intermediate phenotype, plaque calcification. We highlight this point since it can be crucial for the prognosis and therapy of the asymptomatic population.

Inter-relation between hypoxic liver injury and killip classification in st segment elevation myocardial infarction patients

Abstract Purpose Hypoxic liver injury (HLI) and Killip classification are poor prognosticators of ST segment elevation myocardial infarction (STEMI) patients. We investigated the inter-relationship between hypoxic liver injury (HLI) and Killip classification. Materials and Methods 4 tertiary hospitals from Incheon-Bucheon province enrolled 1537 STEMI patients who had undergone percutaneous coronary intervention (PCI) from 2007 to 2014. They were divided into 4 groups according to their Killip classification presented at the emergency room (ER). HLI was defined as ≥2-fold increase of serum aspartate transaminase (AST). Results Incidence of HLI showed incremental tendency with respect to Killip classification (19.5%, 19.4%, 34.6%, 37.8%, p<0.001) respectively. Left ventricular ejection fraction (LVEF) was below 45% in symptomatic, overt heart failure patients (Killip class II, III and IV). Initial and peak AST level increased in accordance to Killip classification along with cardiac biomarkers. In-hospital mortality and Killip classification were in direct relation (2.3%, 7.3%, 16.3%, 29.2%) with statistical significance. Univariate and multivariate Cox regression analysis showed that both presence of HLI and combined Killip classification III and IV were poor prognosticators even after adjusting for conventional clinical risk factors. Receiver operating characteristics (ROC) analysis showed that combination of HLI and Killip classification was the most sensitive predictor of mortality (AUC 0.832, 95% CI 0.78-0.882). Kaplan-Meier curve showed that patients with HLI were at higher risk of death in both Killip class (I+II) and Killip class(III+IV) group. Conclusions Presence of HLI and Killip classification were in direct-relation translating to worst prognosis. Early recognition of HLI and thorough detection of accurate Killip classification is warranted whilst treating STEMI patients.

Potential Role of the Skin in Hypertension Risk Through Water Conservation.

Previous basic and clinical investigations have identified various pathogenic factors and determinants of risk that contribute to hypertension. Nevertheless, the pathogenesis of hypertension has not been fully elucidated. Moreover, despite the availability of antihypertensive medications for the management of blood pressure, treatments that address the full spectrum of the pathophysiological defects underpinning hypertension remain to be identified. To further investigate the mechanisms of primary hypertension, it is imperative to consider novel potential aspects, such as fluid management by the skin, in addition to the conventional risk factors. There is a close association between body fluid regulation and blood pressure, and the kidney, which, as the principal organ responsible for body fluid homeostasis, is the primary target for research in the field of hypertension. In addition, the skin functions as a biological barrier, potentially contributing to body fluid regulation. In this review, we propose the hypothesis that changes in skin water conservation are associated with hypertension risk based on recent findings. Further studies are required to clarify whether this novel hypothesis is limited to specific hypertension or applies to physiological blood pressure regulation.

Triglyceride levels predict high-risk coronary artery plaque progression in asymptomatic patients with type 2 diabetes and normal LDL cholesterol

Abstract Background Type 2 diabetes mellitus (T2D) is associated with an increased risk of coronary artery disease (CAD) and a significant residual risk remains despite management of conventional risk factors. Purpose The purpose of the present study was to assess the association of triglycerides and high-risk plaque progression in patients with asymptomatic T2D without known CAD. Methods Asymptomatic patients with T2D and no history of CAD were studied with serial computed tomography angiography with an inter-scan interval of 13 ± 0.8 months. The total atheroma volume (TAV), and plaque composition (dense calcium, fibrous, fibrous-fatty, and necrotic core plaque) were assessed at baseline and at follow-up. Lipid status was assessed at baseline and after a one-year follow-up. Patients were divided into two groups depending on progression in triglyceride (TG) levels (TG+) and regression of TG levels (TG-). Results Of the 261 patients who were enrolled, 209 patients (157 men and 52 women) were included in the final analysis. Based on changes in TG levels, 107 patients were categorized as (TG+) and 102 patients were categorized as (TG-). The mean age was 62 ± 10 years, and the mean diabetes duration was 11 ± 8 years. At baseline, 76 % of the patients received lipid-lowering treatment, and low-density lipoprotein (LDL) cholesterol was 2.0 ± 0.8 mmol/L. A significantly higher progression of TAV was observed in patients with TG+ compared to TG- (50.2 ± 144.3 vs. -28.5 ± 176.9 mm3, P<0.001). This observation was primarily driven by an increase of fibrous fatty plaque (8.6 ± 41.2 vs. -12.8 ± 39.2 mm3, P<0.001) and necrotic core plaque (-3.9 ± 51.4 vs. -23.7 ± 71.8 mm3, P=0.002). Furthermore, an increase in TG levels predicted rapid plaque progression independent of LDL and other risk factors (OR 1.36, 95% CI; 1.02 – 1.81, P=0.04). Conclusion Changes in TG levels are associated with the progression of total and high-risk plaque volumes in asymptomatic patients with T2D and well-controlled LDL cholesterol.Low attenuation plaque vs. triglycerides

Pulse wave velocity has an additive prognostic value to SCORE2 in apparently healthy subjects at 6 years of follow up

Abstract Backround/Aim: Arterial stiffness is involved in the clinical course of atherogenesis. The purpose of this study was to investigate whether altered arterial wall properties of confers predictively and additively to estimation of cardiovascular risk. Methods Pulse wave velocity carotid-femoral (PWVc-f), the gold standard method to assess arterial stiffness, was measured non-invasively by Complior device. Increased PWV(c-f), especially above 10 m/s, indicates increased arterial stiffness. We measured baseline PWV(c-f) in 747 apparently healthy subjects (51.99±13.41 years old, 43.8% males), without established cardiovascular disease and calculated SCORE2 in each subject according to ESC guidelines.We prospectively monitored the occurrence of major cardiovascular events (MACEs-death, myocardial infarction, stroke) during a 6-year follow-up period using electronic records and clinic visits. Results Fifty-seven MACEs were documented during follow-up. In univariate analysis, subjects with increased PWV were found to exert greater risk for MACEs (hazard ratio (HR):1.12, 95%CI: 1.09-1.15, p<0.001). PWV remained a significant predictor for MACEs in a model including sex, age, hyperlipidemia, diabetes, hypertension, current smoking, family history of coronary artery disease and treatment with ACEi/ARBs or lipid lowering agents after using backward elimination (HR:1.13; 95% CI: 1.08-1.18, p<0.001). PWV was an independent and additive predictor of outcome when added in a model including solely SCORE2 (HR:1.10; 95% CI: 1.07-1.14,p<0.001; Chi-square change:20.08, p<0.001; C-statistic increase from 0.592 to 0.685) and also in a model encompassing risk factors not included in SCORE2, namely diabetes (HR:1.07; 95% CI: 1.04-1.11,p<0.001; Chi-square change: 43.12, p<0.001; C-statistic increase from 0.613 to 0.698). The HR of PWV for the prediction of MACE remained similar in subjects younger or older than the age of 50 years (p>0.05). Conclusion Arterial stiffness is an independent and additive predictor to conventional risk factors and SCORE2 for adverse outcome at 6 years follow-up.

Role of Glycosuria in SGLT2 Inhibitor-Induced Cardiorenal Protection: A Mechanistic Analysis of the CREDENCE Trial.

SGLT2 inhibitors have been shown to provide pronounced reductions in cardio-renal outcomes, including cardiovascular death, heart failure, and renal failure. The mechanisms underlying these benefits remain uncertain. We hypothesized that the effects could be attributed to the elevated glycosuria induced by these drugs. Urine concentrations of glucose, creatinine, and ketones were measured at baseline and after 1-year treatment with either placebo or canagliflozin 100mg/day in ∼2600 individuals from the CREDENCE trial (enrolling patients with type 2 diabetes, chronic kidney disease, and albuminuria). Associations between glycosuria and the primary composite endpoint from CREDENCE and secondary outcomes were assessed using Cox proportional hazards models. Canagliflozin treatment increased fractional urinary glucose excretion from 3±9% at baseline to 30±26% at year 1 (vs 5±19% with placebo, p<0.001). Subjects on canagliflozin and in the top quartile of urine glucose/creatinine ratio at year 1 were significantly protected for the primary endpoint (HR=0.42 [95% C.I.:0.30-0.61]); similar results were seen for hospitalized heart failure (HR=0.45 [0.27-0.73]) and all-cause death (HR=0.56 [0.39-0.80]). These associations persisted on adjustments for multiple conventional risk factors. In patients with T2D and CKD treated with canagliflozin, individuals with the highest amount of glycosuria showed the strongest protection against multiple cardio-renal outcomes.

Abstract 16988: Conventional and Regionally Distinctive Risk Factors for First-Onset Myocardial Infarction in Bangladesh. The Bangladesh Risk of Acute Vascular Events (BRAVE) Study

Background: South Asians may be particularly susceptible to premature myocardial infarction (MI) owing both to classic cardiovascular risk factors and distinctive practices more common in South Asian populations. Hypothesis: Identifying modifiable risk factors for MI in South Asian populations should inform prevention strategies. Goal: To study conventional risk factors and several distinctive South Asian characteristics and practices in relation to the likelihood of first-ever MI in Bangladesh. Methods: In a case-control study involving 8,133 first MI cases and 8,122 controls, we calculated odds ratios (ORs) for MI (adjusted, when appropriate, for age, sex, smoking status, history of diabetes, history of hypertension, family history of MI, and LDL-cholesterol) and assessed their potential public health impact using population attributable fractions (PAFs). Results: The mean (SD) age of first MI was 53 (11) years. Adjusted ORs (95% CIs) were 2.75 (2.53-2.99) for cigarette smoking, 2.33 (2.08-2.60) for parental history of MI, 2.26 (2.07-2.48) for history of hypertension, 1.79 (1.61-1.98) for history of diabetes, and 1.61 (1.55-1.67) per 1-SD higher LDL-cholesterol. The highest PAFs (95% CIs) were for current cigarette smoking (48.9% [46.1%-51.6%]), higher LDL-cholesterol (32.4% [30.2%-34.4%]) and history of hypertension (14.7% [13.2%-16.1%]). As for regionally distinctive practices, ORs were 4.05 (3.15-5.21) with biri smoking, 2.04 (1.48-2.81) with chewing tobacco, and 1.26 (1.05-1.51) with parental history of first cousin marriage. Conclusion: In a large case-control study, we confirmed the relevance of several conventional risk factors to risk of first-onset MI in the Bangladesh population. We also identified significant associations with MI of practices distinctive to South Asian populations, including indigenous modes of tobacco consumption and parental first-cousin marriage, apparently independent of conventional risk factors. These findings should help identify opportunities for cardiovascular disease prevention in South Asia that embrace both conventional and regionally distinctive risk factors.

Abstract 15063: Incidence and Risk Factors for Heart Failure in 20 000 Newly Diagnosed Diabetes Patients

Introduction: Heart Failure (HF) is a diabetes complication causing high mortality and morbidity but has received relatively limited attention compared to other complications such as acute myocardial infarction (AMI). Substantial residual HF risk remains after achieving current treatment targets, suggesting important additional pathophysiological mechanisms beyond conventional risk factors. Aim: to study the incidence and risk factors for HF in newly diagnosed diabetes patients. Methods: We used a contemporary, regional inception cohort (n=19,938) from Scania County in Sweden, to study the incidence and risk factors for HF from initial diabetes diagnosis. Biochemical and questionnaire data were collected within 1 year from initial diagnosis in newly diagnosed diabetes patients (&gt;90% participation rate). We combined baseline data with information on incident HF and AMI diagnoses from a nationwide patient register, and applied Cox-regression models for analysis. Results: A total of 819 patients (4%) had been diagnosed with HF before diabetes diagnosis (median 3 years earlier) and 1245 (6%) with AMI. The cumulative incidence of HF in patients free from HF at diabetes diagnosis was 5%, similar to AMI (3%), during up to 13 years follow-up (median 5 years). Of patients with incident HF, 27% had a prior AMI. No type 1 diabetes (T1D) patient had incident HF, while HF risk was similar in type 2 diabetes, latent autoimmune diabetes in adults (LADA) and secondary diabetes. In non-T1D diabetes patients, male sex (HR 1.52) and higher age at onset (HR 1.08), BMI (HR 1.04), and insulin resistance (HR 1.17) were independently associated with higher incidence of all-cause HF and HF without prior AMI (p&lt;0.05). Baseline fasting glucose, HbA1c and autoantibodies were not associated with HF. Conclusions: Our findings demonstrate high incidence of HF over the decade after initial diabetes diagnosis, comparable to AMI. We further identify insulin resistance, but not hyperglycemia or autoantibodies, as risk factor for HF.

Abstract 14681: Coronary Artery Calcium is Associated With Cardiovascular Disease and Poorer Survival in Patients Undergoing Autologous Hematopoietic Cell Transplantation

Background: Hematopoietic cell transplantation (HCT) is an established curative treatment for patients with hematologic malignancies, however survivors are at a &gt;4-fold risk of cardiovascular disease ([CVD] heart failure, myocardial infarction, stroke]) compared to the general population. Coronary artery calcium (CAC) is predictive of CVD in non-oncology patients; less is known about its association with CVD risk and outcomes after HCT. Methods: This was a retrospective cohort study of 243 consecutive patients who underwent first autologous HCT for Hodgkin/non-Hodgkin lymphoma between 2009-2014 with no history of CVD. CAC was determined from chest computed tomography performed &lt;60d from HCT; measurements (Agatston unit) were made by trained researchers blinded to patient demographics and outcomes. CAC was categorized as: 0, 1-100, &gt;100. Multivariable Cox regression analysis was used to calculate hazard ratio (HR) estimates and 95% confidence intervals (CI), adjusted for covariates (age, conventional risk factors [e.g. hypertension, dyslipidemia], cancer treatment). Results: Median age (range) at HCT was 55.7y (18.5y-75.1y), 59% were male; race/ethnicity: non-Hispanic white (60%), Hispanic (25%), Asian (11%), Black (4%); prevalence of CAC was 37%. The 5y CVD incidence for the cohort was 12%, and there was an incremental increase according to CAC score: 0 (6%), 1-100 (20%), &gt;100 (32%); p=0.001 (Figure 1A). CAC was significantly associated with CVD risk (HR 3.0, 95%CI 1.2-7.5) and worse 5y survival (77% vs. 50% p&lt;0.001 [Figure 1B]; HR 2.0, 95%CI 1.1-3.4), compared to those without CAC. Conclusions: CAC is an important and independent predictor of CVD and survival after HCT. Taken together, these data form the basis for integration of readily available imaging information into decision making prior to HCT (e.g. pre-habilitation, non-HCT approaches) or after HCT (e.g. cardiac rehabilitation), setting the stage for strategies to optimize outcomes after HCT.

Abstract 18812: Premortem Risk Assessment Among Countywide Sudden Deaths

Introduction: Heart failure (HF) and left ventricular ejection fraction (EF) assessment have been hallmarks of sudden cardiac death (SCD) risk stratification for over 20 years. However, their sensitivity, specificity, and positive predictive value (PPV) for true arrhythmic death in the general population are unknown because nearly all SCD studies presume arhythmic causes. Aims: To define sensitivity, specificity, and PPV of current SCD risk stratification criteria for the autopsy-confirmed arrhythmic cause among countywide sudden deaths. Methods: POST SCD (POstmortem SysTematic Investigation of Sudden Cardiac Death) is a prospective cohort study using autopsy, clinical records, and toxicology to adjudicate arrhythmic (SAD; potentially rescuable with implantable defibrillator) or non-arrhythmic (non-SAD; e.g., tamponade, overdose) causes among presumed SCDs (pSCDs) in San Francisco County. We analyzed sensitivity, specificity, and PPV for syncope, EF≤35%, diagnosed HF, or the presence of any of 3 factors to discriminate SADs among pSCDs. Results: Between February 2011 and September 2022, 845 of 904 (93%) pSCDs 18-90 years had complete medical records available, of which 491 (58%) were SADs. Seventy-three pSCDs had history of syncope, with similar prevalence in SADs and non-SADs (p=0.4), while prevalence of HF was higher in SADs vs. non-SADs (88/491[18%] vs. 39/354 [11%], p=0.003). EF assessment was performed in 206 pSCDs (24%, 133 SADs, 73 non-SADs); prevalence of EF ≤ 35% was similar between SADs and non-SADs (p=0.112). A greater proportion of SADs had ≥1 factor than non-SADs (122/491[25%] vs. 65/354 [18%], p=0.015). Sensitivity of syncope, EF≤35%, HF, ≥1 factor for SAD was 9, 26, 17, 25%, specificity was 92, 82, 90, 82%, and PPV was 60, 73, 69, 65%, respectively. Conversely, 369 of 491 (75%) SADs had no risk factors before sudden death. Defibrillators were implanted in 4/491 (0.8%) SADs. Conclusions: In this 11-year countywide postmortem study, conventional risk factors had low sensitivity and PPV but high specificity for autopsy-confirmed arrhythmic cause of sudden death. Three-fourths of SADs had no risk factors before sudden death, highlighting the need for improved risk prediction in the general population.

Abstract 14532: The Off-Hour Effect on Clinical Outcomes of ST-Segment Elevation Myocardial Infarction Complicated by Cardiogenic Shock Patients Treated With Impella: Insight From Japanese Registry for Percutaneous Ventricular Assist Device (J-PVAD)

Introduction: The off-hours effect is a contentious issue in that patients admitted on weekends or nighttime have worse outcomes than on weekday daytime. The off-hours effect in patients with ST-segment elevation myocardial infarction complicated by cardiogenic shock (STEMI-CS) treated with Impella has not been fully evaluated. Hypothesis: The off-hours admission is associated with longer door-to-unload (DTU) time, door-to-balloon (DTB) time, and higher mortality in this population. Methods: We used the Japanese large-scale registry data for Percutaneous Ventricular Assist Device (J-PVAD), which registered all consecutive patients treated with Impella from December 2019 to July 2022. We compared the effects of on-hours and off-hours admissions on DTU time, DTB time, and 30-day mortality. We defined “on-hours” as between 8:00 and 19:59 on weekdays and the other time as “off-hours”. A multiple linear regression model was used to reveal the independent factors of prolonged DTU and DTB times. The Cox proportional hazards model was applied to calculate adjusted hazard ratios [aHR] for 30-day mortality, controlling for conventional cardiac risk factors. Results: Of 2,453 patients, 775 (32%) (mean age 68 years, 628 (81%) male) STEMI-CS patients treated with Impella were included. Among them, 401 (39%) were admitted during off-hours. We observed 155 deaths (49%) among patients admitted off-hours and 134 deaths (36%) among patients admitted on-hours during the follow-up period (median: 23 days). The DTU and DTB times were significantly longer in patients admitted off-hours than in patients admitted on-hours (91 (IQR 74-164) vs. 74 (62-151) minutes, p&amp;lt;0.001; 104 (77-134) vs. 89 (61-122), p&amp;lt;0.001, respectively). The linear regression model showed that the off-hours admission was associated with longer DTU time (β=14.3 minutes, 95% CI 4.8-23.8, p=0.003) and DTB time (15.4, 5.0-25.7, p=0.004). The Cox proportional hazards model showed that off-hours admission was associated with a higher risk of 30-day mortality than on-hours admission (aHR=1.42, 95% CI: 1.03-1.96, p=0.03). Conclusion: Our findings implied that the off-hours effect existed in DTU time, DTB time, and 30-day mortality among STEMI-CS patients treated with Impella.

Association of Adipokines with Alzheimer's Disease in a Chinese Cohort.

The correlation between plasma adipose factor levels and Alzheimer's patients is not entirely clear. We aimed to investigate associations between AD and plasma levels of three adipokines including plasma adiponectin, leptin, and resistin. A single-center, cross-sectional study recruited AD patients (n = 148) and cognitively normal (CN) controls (n = 110). The multivariate logistic regression analysis was applied to determine associations of adiponectin, leptin, and resistin with the presence of AD. The receiver operating characteristic (ROC) analysis was employed to determine the diagnostic power of adiponectin, leptin and resistin for AD. After adjusted for the conventional risk factors, plasma levels of leptin (OR = 0.417, 95% CI: 0.272-0.638, p < 0.0001) and adiponectin (OR = 1.249, 95% CI: 1.151-1.354, p < 0.0001) were associated with the presence of AD. In total participants, the plasma adiponectin level was negatively correlated with MMSE scores (p < 0.0001) and was positively with CDR scores (p < 0.0001) and age (p < 0.0001). The plasma level of leptin was negatively correlated with CDR scores (p < 0.0001) and positively correlated with MMSE scores (p < 0.0001). Both adiponectin (p < 0. 0001) and leptin (p < 0. 0001) featured higher AUC than the random chance. Plasma adiponectin and leptin were associated with the presence, symptomatic severity, and diagnostic power of AD, suggesting a potential role of adipokines in the pathogenesis of AD.

Abstract 11965: Impact of Atherothrombotic Risk Stratification in Patients With Heavily Calcified Lesions Following Rotational Atherectomy

Background: Patients who undergo percutaneous coronary intervention (PCI) with rotational atherectomy (RA) are at high risk of adverse clinical outcomes, and there are few clinical risk stratification tools for these patients. The Thrombolysis in Myocardial Infarction Risk Score for Secondary Prevention (TRS 2°P) is a simple 9-point risk stratification tool. A previous study reported that TRS 2°P was useful in predicting adverse clinical events in patients with acute coronary syndrome. However, it is unclear whether TRS 2°P predicts adverse clinical events in patients with heavily calcified lesions, requiring RA. Hypothesis: This study aimed to investigate whether TRS 2°P is useful for the prediction of adverse clinical events in patients undergoing PCI with RA from the Japanese multicenter PCI registry. Methods: We conducted a study with 196 patients who underwent PCI with RA out of 7,391 patients who underwent PCI in a multicenter, prospective cohort registry. Patients were divided into 3 groups according to the tertiles of the TRS 2°P: 65 patients in the T1 group (TRS 2°P&lt;3), 66 patients in the T2 group (TRS 2°P=3), and 65 patients in the T3 group (TRS 2°P&gt;3). The primary endpoint was the cumulative 2-year incidence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as a composite of cardiac death, acute coronary syndrome, and ischemic stroke. Results: A cumulative 2-year MACCE occurred in 41 (24%) patients during the follow-up period. The cumulative incidence of MACCE was significantly higher in the T3 group than in T1 group (log-rank p=0.02). Multivariate Cox analyses revealed that the T3 group was associated with an increased risk of MACCE compared to T1 group (adjusted hazard ratio, 2.66; 95% confidence interval, 1.04–6.77; p=0.04). The addition of TRS 2°P to conventional risk factors, including male sex, number of diseased vessels, and low-density lipoprotein cholesterol levels, improved the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) (NRI 0.39, p=0.027; IDI 0.072, p&lt;0.001). Conclusions: Atherothrombotic risk stratification using TRS 2°P is useful for identifying high-risk patients with heavily calcified lesions following RA.

Abstract 13573: Association of Increased Eicosapentaenoic Acid to Arachidonic Acid Ratio With Early Restoration of Coronary Blood Flow in ST-Elevation Myocardial Infarction

Background: Early restoration of coronary blood flow is important to reduce myocardial damage in patients with ST-elevation myocardial infarction (STEMI). Cardiovascular protection of increased levels of eicosapentaenoic acid (EPA) to arachidonic acid (AA) has been shown in recent clinical trials. Therefore, this study examined whether increased EPA / AA ratio was related to early restoration of coronary blood flow in STEMI patients underwent primary percutaneous coronary intervention (PCI). Methods: Serum levels of EPA, AA, and EPA/AA ratio were measured in consecutive 216 STEMI patients. The angiographic findings of TIMI-flow grade in the infarct related artery before PCI were compared between patients with and without increased EPA / AA ratio (&amp;gt;0.291). Results: TIMI-flow grade 3 before PCI were obtained in 25 (11.6%) of all study patients. Smaller enzymatic infarct size was obtained in patients with TIMI-flow grade 3 before PCI compared with TIMI-flow grade 0-2 before PCI (Peak CK-MB; 358 &amp;plusmn; 252 mg/dL, vs. 280 &amp;plusmn; 260 mg/dL, p &amp;lt;0.05). There were significant differences between 2 groups in the distribution of TIMI-flow grade (p&amp;lt;0.05). Moreover, multivariate logistic regression analysis showed that patients with increased EPA/AA ratio was significantly associated with the presence of TIMI-flow grade 3 before PCI after adjustment for conventional risk factors (OR 5.0, 95% CI 1.92-12.8, p&amp;lt;0.01). Conclusions: Increased levels of EPA /AA ratio is independently associated with early restoration of coronary blood flow, leading to reduced myocardial damage in patients with STEMI. These results might support the new strategy of administration of EPA before PCI in STEMI care.

Abstract 16712: Cardio-Ankle Vascular Index as an Independent Predictor of Cardiovascular Events in Patients With and Without Previous Cardiovascular Disease: A Systematic Review and Meta-Analysis

Background: Large artery stiffness predicts the risk of major adverse cardiovascular events (MACE). However, most data to date are related to carotid-femoral pulse wave velocity. Data about the prognostic value of cardio-ankle vascular index (CAVI), a less blood pressure-dependent marker, are limited, especially among individuals without prior cardiovascular disease (primary prevention). Hypothesis: Higher baseline CAVI is associated with incident MACE and all-cause death. Methods: PubMed, Scopus, and Web of Science were searched up to 29 April 2023 for longitudinal studies reporting the association of CAVI with incident fatal and nonfatal cardiovascular events. Risk of bias was assessed using the MINORS tool. Pooled hazard ratios were calculated separately based on use of CAVI as a categorical or continuous variable. Subgroup analysis focused on studies of patients without prior cardiovascular disease. Results: We included 21 studies (37,658 participants; mean age range 52-75 years; 53.9% males). Median study follow-up duration was 5 years (IQR 4.4-6; range 2-12.4). Despite variations in multivariable models, studies reported adjustments for conventional risk factors. Higher CAVI was associated with risk of MACE among all studies (categorical HR=1.45 [1.23-1.70], I 2 =51%; continuous HR=1.24 [1.15-1.33], I 2 =18%) and in primary prevention studies (categorical HR=1.48 [1.12-1.96], I 2 =67%; continuous HR=1.22 [1.12-.33], I 2 =25%). While CAVI was associated with all-cause mortality in the overall analysis (HR=1.34; 95% CI: 1.09-1.63, I 2 =41%), primary prevention studies did not show a significant association (HR=1.09; 95% CI: 0.9-1.32 I 2 =15%). Conclusion: CAVI holds promise as an independent predictor for MACE, including individuals without established cardiovascular disease. Further epidemiological studies are needed to better understand its prognostic role, normative values in different groups, and its role in primary prevention strategies.

Identification of an association between coronary heart disease and ITGB2 methylation in peripheral blood by a case-control study

BackgroundBlood DNA methylation was associated with coronary heart disease (CHD) risk in Caucasians. We investigated the association between DNA methylation in peripheral blood at the reported loci and CHD in the Chinese population. MethodsThe integrin subunit beta 2 (ITGB2) gene was identified in 196 CHD cases and 184 controls, and its methylation level was determined by mass spectrometry. Logistic regression was used to assess the association. ResultsHypomethylation of ITGB2 was significantly associated with heart failure CHD and NYHA Ⅰ&Ⅱ CHD patients with minor to medium cardiac function impairment (ITGB2_CpG_11/cg08422803, OR per −10 % methylation = 1.15 and 1.16; p = 0.012 and 0.018 by Bonferroni correction, respectively). Hypomethylation of ITGB2_CpG_11/cg08422803 was a risk factor for CHD in people < 65 years and males (p < 0.05 after Bonferroni correction). The combination of ITGB2 methylation and conventional CHD risk factors could efficiently discriminate CHD, heart failure CHD, NYHA I&II CHD, and myocardial infarction CHD patients from controls (AUC = 0.78, 0.81, 0.80, and 0.81, respectively). ConclusionBlood-based ITGB2 methylation has the potential as a biomarker for CHD. The combination of ITGB2 methylation and conventional CHD risk factors may improve the risk assessment and detection of CHD.

ELN Criteria for Cytoreduction Start Identify Patients with Polycythemia Vera at Higher Thrombotic Risk

Introduction Recently, the European Leukemia Net (ELN) recommended cytoreduction in patients (pts) with Polycythemia Vera (PV) at low risk (LR) (age &amp;lt;60 yrs &amp; no previous thromboses) but carrying additional criteria for therapy start (CTS) ( Marchetti M et al, Lancet Haematol 2022). Little is known about: 1] efficacy of hydroxyurea (HU) in LR pts, high risk due to age &amp;gt;60 yrs (HR-AGE) or high risk due to previous thrombosis regardless of age (HR-THRO); 2] impact of CTS on thrombotic risk. Aims In a large cohort of HU-treated PV pts, we investigated if thrombotic risk was influenced by: 1] conventional risk factors for thrombosis; 2] ELN-defined complete response (CR) at 12 mos; 3] presence of CTS. Methods After IRB approval, data of 961 WHO2016-defined PV pts were retrospectively collected by 21 Hematology Centers. In April 2023, an update was performed in 10 participating Centers with specific focus on CTS at diagnosis and HU start; 504 HU-treated pts resulted eligible for this analysis. Therapy was at discretion of the treating hematologist. Pts were followed until death or data cut-off date. CTS evaluated for association with thrombosis included: persistent/progressive leukocytosis (100% increase if white blood cells (WBC) &amp;lt;10 x10 9/L or 50% increase if WBC&amp;gt;10 or WBC&amp;gt;15 at diagnosis and HU start); extreme persistent thrombocytosis (&amp;gt;1000 x10 9/L platelets (PLT) at diagnosis and HU start); progressive splenomegaly (increase of &amp;gt;5 cm from diagnosis); inadequate hematocrit (Hct) control (&amp;gt;6 PHL/yr; HCT &amp;gt;53% at diagnosis and HU start; PHL intolerance); uncontrolled cardiovascular risk factors (CVRF). Symptoms were present as the only ELN criterion in 40 patients, of whom none had thrombosis; therefore, they were not included in the analysis. Results 504 pts received HU: 81 pts were at LR and 423 (83.9%) were at HR (HR-AGE, no. 290, 57.5%; HR-THRO, no. 133, 26.4%). Median time on HU was 11.6 yrs (0.1-23.1). During HU, 53 pts had 69 thromboses (35 arterial) for an incidence rate of thrombosis (IR-thro) of 1.5 %p-y, comparably in LR and HR ( Table 1). Notably, IR-thro was equal in LR and HR-AGE (p=0.94), but significantly higher in HR-THRO pts (p=0.005 vs LR and p=0.009 vs HR-AGE). At 12 months, CR was achieved by 8.2%, 23% and 25% of LR, HR-AGE and HR-THRO pts, respectively (LR vs HR-AGE and HR-THRO, p&amp;lt;0.001 and p=0.003). Thrombosis-free survival (TFS) by landmark analysis at 12 months was significantly better in CR pts (p=0.01). Specifically, best TFS was observed in LR and HR-AGE pts with CR, while HR-THRO pts without CR had the worst TFR (p=0.009). CTS were observed in 255 (50.6%) pts: 48 LR (59.3%), 139 HR-AGE (47.9%) and 68 HR-THRO (51.1%). In the remaining LR pts, HU was triggered by mild thrombocytosis (&amp;lt;1000 x10 9/L) and/or mild leukocytosis (&amp;lt;15 x10 9/L) and/or mild splenomegaly (&amp;lt;5 cm from costal margin) and/or persistent systemic symptoms. CTS were associated to significantly increased of IR-thro in the overall cohort (p&amp;lt;0.001), in LR pts (p=0.04), in HR-AGE pts (p=0.02) and in HR-THRO pts (p=0.03) ( Table 1) . The impact of CTS was confirmed in the overall cohort both for arterial (1.30 vs 0.44 %p-y, p=0.01) and venous thrombosis (1.37 vs 0.44 %p-y, p=0.007). TFS at 5 yrs was 87% and 95% in pts with or without CTS (p&amp;lt;0.001) ( Fig.1a). In presence of CTS, TFS of LR and HR-AGE pts were comparable to HR-THRO pts without CTS ( Fig. 1b). In multivariate Cox analysis considering age&amp;gt;60 yrs, previous thrombosis, CTS, and CR to HU at 12 months, CTS and previous thrombosis remained associated with thrombotic risk (HR: 2.7, 95% CI: 1.4-5, p =0.002; HR: 2.4, 95% CI: 1.4-4.2, p =0.001). Finally, in 59 additional LR pts untreated with HU, IR-thro was 0.78 in absence of CTS, and 1.57 %p-y in presence of such criteria. Conclusions Albeit retrospective, this study shows for the first time that ELN criteria for therapy start including splenomegaly, leukocytosis, thrombocytosis, uncontrolled Hct and CVRF, identified an increased risk phenotype either in LR and HR pts treated with HU. This was confirmed also in HU-untreated pts. Also, lack of CR at 12 months was detrimental on TFS particularly in HR-THRO pts, and less significantly than CTS. These findings, that complement data from the Majic-PV trial ( Harrison CN et al, J Clin Oncol 2023), dictate better management of HU therapy, and call for greater attention to CTS and their integration into prognostic models that go beyond the two categories related only to age and thrombotic history.

Stronger Associations of TyG Index with Diabetes Than TyG-Obesity-Related Parameters: More Pronounced in Young, Middle-Aged, and Women.

The triglyceride glucose (TyG) index and TyG-related indicators have been proposed as a marker of insulin resistance. It is unclear which is the best indicator to predict diabetes mellitus (DM) in Chinese. This study aimed to investigate the predictive value of different biomarkers for the incidence of DM. Between January 2017 and December 2020, 5575 subjects who underwent health examinations in Hebei General Hospital were retrospectively included. The primary endpoint was new onset DM. During a median follow-up of 3.03 years, 133(2.39%) individuals developed DM. Multivariable cox proportional hazards models revealed that TyG index and TyG-related parameters were positively associated with DM risk. As the interaction analyses showed, there were significant interactions with sex and age levels in relation to DM risk (both P for interaction <0.05). Risk prediction for DM was significantly improved by adding TyG index to the baseline model using conventional diabetic risk factors in predicting DM at follow-up. This population-based cohort study suggested a causal relationship between TyG index and DM after adjusting for other confounding factors. This independent and significant association was more apparent in females and subjects younger than 65 years. Compared with the TyG-BMI, TyG-WC, TyG-WHtR, the TyG index was a more effective predictor of DM.