Occurrence Of Cardiovascular Events Research Articles

Long-term monocyte activation after coronary artery bypass grafting: an exploratory prospective observational study

Major surgery such as coronary artery bypass grafting (CABG) is associated with an increased post-operative risk of atherosclerotic cardiovascular events. Cells of the innate immune system can adopt a long-lasting pro-inflammatory and atherogenic phenotype after brief exposure to exogenous or endogenous inflammatory stimuli, a process called “trained immunity”. We hypothesized that the surgery-induced inflammation leads to sustained alterations in monocyte function, which promote the subsequent occurrence of cardiovascular events. Blood from 13 patients undergoing elective CABG was obtained before, 3-7 days (median 4) after, and 6-8 weeks (median 6) weeks after surgery. At 3-7 days postoperatively, circulating C-reactive protein (CRP) concentration, leukocyte counts and ex vivo Peripheral Blood Mononuclear Cell (PBMC) IL-6, TNFα and IL-1Ra production after stimulation (with various inflammatory stimuli) were significantly increased. Simultaneously, there was a reduction in monocyte HLA-DR expression. 6-8 weeks after CABG there was an ongoing systemic pro-inflammatory state with higher CRP concentrations, increased stimulated ex vivo PBMC IL-6 production, changes in monocytes subsets, and a higher expression of CCR2 on monocytes compared to baseline. In conclusion, CABG induces a persistent systemic inflammatory reaction with a sustained activated monocyte phenotype. This might contribute to the increased atherosclerotic cardiovascular event risk observed in cardiac surgery patients.

The impact of daily step count with mobile health apps on clinical outcomes among general population

Abstract Background/Introduction Numerous studies have investigated the correlation between daily step count and the reduction of all-cause mortality and cardiovascular events. However, the optimal daily step count for the general population remains controversial. Purpose This study aims to assess cardiovascular risk based on individual step counts using a large cohort that includes step count data from mHealth Apps (Kencom), health checkups databases, and Japanese insurance claims databases. Methods We analyzed data from 85,204 users registered with Kencom between January 2016 and September 2021. The mean step count during one year before and after baseline data collection was used to define each individual's step count. We divided participants into low (N=45,539) and high (N=39,665) step count groups based on their mean step counts. Additionally, we categorized users into five groups based on their step counts (<4000; 4000-5999; 6000-7999; 8000-9999; and ≥10000) to evaluate cardiovascular events. The primary outcome was the occurrence of cardiovascular events, including myocardial infarction, stroke, angina pectoris, heart failure, and atrial fibrillation, as classified by the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The cumulative incidence was estimated over 5 years. Results The high step count group was generally younger and predominantly male. No significant differences in cardiovascular risk factors such as hypertension, dyslipidemia, diabetes mellitus, and current smoking status were found between the two groups. Stratifying baseline characteristics by step count revealed significant differences among the five groups, with the exception of sex. The cumulative incidence of cardiovascular events was significantly lower in the high step count group compared to the low step count group (6.5% vs. 7.5%, log-rank P=0.005, Figure 1). After adjusting for confounding factors, the risk reduction of the high step count group remained significant (HR: 0.92, 95% CI: 0.87-0.98, P=0.005). Among the five step count groups, the incidence of primary outcome significantly differed, with only Group 5 (≥10000 steps) showing a significant reduction in the risk of cardiovascular events compared to Group 1 (<4000 steps) after adjustment (HR: 0.87, 95% CI: 0.77-0.99, P=0.03). Subgroup analyses based on sex indicated that the risk reduction was significant in males in Group 5 but not in females. Conclusion The risk of cardiovascular events was higher in the low step count group compared to the high step count group. After adjusting for confounders, only the highest step count group (≥10,000 steps/day) showed a significant reduction in cardiovascular event risk compared to the lowest step count group.

Predictive value of Type D personality combined with unhealthy cardiovascular behaviors for the long-term adverse cardiovascular events in ACS patients

Abstract Background Acute coronary syndrome (ACS) has become a major public health problem worldwide due to its high morbidity and mortality. In addition to traditional risk factors, psychosocial factors play an important role in the development of ACS.Type D personality, as a combination of social inhibition and negative affect, has been defined as a psychological risk factor for coronary heart disease by the European Society of Cardiology.Meanwhile, ACS patients with Type D personality may have behaviors such as unhealthy dietary behaviors, less regular physical activity, and poorer self-management behaviors. Then, whether the combination of Type D personality and poor cardiovascular health behaviors can increase the risk of poor prognosis in patients with ACS requires further research. Purpose The aim of this study was to investigate the effect of Type D personality combined with poor cardiovascular health behaviors on long-term major adverse cardiovascular events(MACE) in patients with ACS. Methods A total of 18631 patients diagnosed with ACS between January 2017 and July 2023 were included in this study. Type D personality, cardiovascular health behaviors (smoking cessation, physical activity, average sleep duration at night, dietary assessment index, BMI, lipids, blood glucose, blood pressure) were assessed during the admission period, and were divided into poor, general, and ideal cardiovascular health with a cut-off score of 50 and 80.The binary logistic regression analysis was used to assese the effect of Type D personality combined with cardiovascular health score on the occurrence of MACE (stroke, reinfarction, revascularization, all-cause death). Results The median follow-up in this study was 37 months, and we found that a total of 3750 people had MACE during the follow-up period. The logistic regression result showed that compared with Type D personality (-) and cardiovascular health behaviors (poor) group, Type D personality (+) and cardiovascular health behaviors (poor) group (OR=1.451, 95%CI=1.055-1.995,P=0.022), Type D personality (+) and cardiovascular health behaviors (general) group (OR=1.425, 95%CI=1.092-1.858,P=0.009), Type D personality (-) cardiovascular health behavior (poor) group (OR=1.301, 95%CI=1.013-1.670, P=0.039) were independent risk factors for the occurrence of further adverse cardiovascular events. Conclusion Type D personality combined with unhealthy cardiovascular behavior individuals may be at high risk for MACE. Therefore, early assessment of Type D personality and cardiovascular health behaviors are needed, thereby reducing the incidence of MACE in ACS patients.

Is the HNF4A gene variant paradoxically associated with better prognostic in CAD patients?

Abstract Background The Hepatocyte nuclear factor 4 A (HNF4A) gene was considered to be associated with susceptibility to atherosclerosis and coronary artery disease (CAD). It encodes a protein HNF4α, a genetic transcription factor regulating the genetic expression of thousands of genes playing essential roles in glucose and lipid metabolism. Its abnormal expression is emerging as a critical factor in diabetes, dyslipidemia, and cancer. Loss of function of specific mutations could attenuate its role in CAD pathogenesis and the progression of atherosclerosis. Aim To investigate whether a genetic variant (HNF4α rs1884613 C>G) could be associated with a low genetic function and, paradoxically, a better prognostic in CAD patients. Methods A cohort of 1,718 patients with coronary angiography (>70% stenosis of at least one main coronary vessel) from the GENEMACOR Study was investigated. Thirty-three genetic variants were genotyped using TaqMan assay methodology and HNF4A rs1884613 C>G genotype models were individually studied regarding the occurrence of Major Adverse Cardiovascular Events (MACEs). We used bivariate analysis to evaluate genotypic and allelic differences. Multivariate Cox regression analysis estimated variables independently associated with MACE, and Kaplan-Meier estimate methodology assessed the survival. Results Of the 1,718 CAD patients with the CC wild type, 73.4% had MACE, compared with 66.5% without. CG had 25.2% compared with 30.5% without. Finally, in the GG genotype, only 1.4% had events compared with 3.0% without (p=0.004). Cox regression analysis showed that GG genotype (mutated) is significantly and independently associated with 56% of MACE protection with a hazard ratio (HR) of 0.436; p=0.014. Physical inactivity and type-2 Diabetes remained independently associated with MACE occurrence (Fig.1). Kaplan-Meier cumulative event analysis disclosed that the carriers of the GG genotype were significantly associated with a better event-free time, and CC discloses a worse event-free time (Breslow test, p=0.001) (Fig.2). Conclusions The rs1884613 genetic variant of HNF4A is associated with a better CAD prognosis. This variant could probably induce gene downregulation and HNF4A gene function loss. Modifying and modulating hepatic lipase and lipid metabolism positively affected atherosclerosis progression. Future bioactive modulators for HNF4A variants could raise the possibility that diseases involving diabetes, lipid disorders, and cancer might be amenable to pharmacologic intervention.

Delirium and risk of incident cardiovascular events in elderly: data from a global health research network

Abstract Introduction Delirium is a common complication of acute medical disorders. A strong association between cardiovascular events and the occurrence of delirium has been recorded. Thus far, no data are available regarding the risk of incident cardiovascular events after delirium onset in older adults. Methods Using data from TriNetX, a global health federated research network, we performed a propensity score matched (PSM) analysis of older adults (age ≥65 years) admitted to the emergency department (ED) reporting delirium within two weeks, who were compared with those without delirium. We evaluated the occurrence of a composite outcome of cardiovascular events (myocardial infarction, ischemic stroke, heart failure, intracranial haemorrhage, ventricular arrhythmias, takotsubo syndrome, and atrial fibrillation) at 30 days and 1 and 3 years of follow-up. Results 4,480,229 patients were retrieved for the analysis, and 82,693 (1.8%) reported delirium. Before PSM, patients reporting delirium were older, with more prevalent comorbidities. After PSM, a total of 165,386 patients were included in the analysis (mean (SD) age 76.6 (9.0) years, 51.1% females). Throughout the entire follow-up period, the cumulative composite cardiovascular events outcome was significantly higher in patients which reported delirium [Red Line, Figure 1]. Delirium was associated with cardiovascular events at 30 days (HR 1.96, 95% CI 1.92-2.00) ,1 year (HR 1.75, 95% CI 1.72-1.78) and 3 years (HR 1.67, 95% CI 1.64-1.69) of follow-up, as well as for each of its components (Table 1). The presence of delirium was also associated with a higher risk of all-cause death and hospital access (Table 1), evaluated as secondary outcomes. In patients with delirium associated with the occurrence of incident cardiovascular events, there was a higher risk of recurrent cardiovascular events at 1 year (HR 3.11, 95% CI 2.92-3.31) and 3 years (HR 2.84, 95% CI 2.67-3.01) of follow-up. Conclusions In a large, unselected cohort of older adults admitted to ED, occurrence of delirium was associated with a higher risk of cardiovascular events, both in the short and long-term follow-up.Figure 1:Delirium and CV EventsTable 1:Cox Regression Analysis

Clinical impact of systemic inflammation across the spectrum of different high-sensitivity CRP values in patients undergoing percutaneous coronary intervention

Abstract Background Systemic inflammation enhances atherosclerosis progression and is a well-established determinant of cardiovascular risk. High-sensitivity C-reactive protein (hsCRP), the most widely available biomarker of inflammation, has indeed been associated with the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients undergoing percutaneous coronary intervention (PCI). However, some heterogeneity exists in the threshold to define high hsCRP associated with increased cardiovascular risk, with the 2 and 3 mg/L cut-offs being used more commonly. Purpose We aimed to evaluate the clinical impact of systemic inflammation in patients undergoing PCI across the spectrum of baseline hsCRP values. Methods We retrospectively evaluated consecutive patients undergoing PCI with drug-eluting stent implantation from 2012 to 2022 at Mount Sinai Hospital (NY, USA). We excluded patients presenting with acute myocardial infarction or active cancer and those for whom baseline hsCRP was not available or was above 10 mg/L. Patients were stratified into three groups according to baseline hsCRP levels: <2.0, 2.0 to 3.0, and >3.0 mg/L. We estimated the risk of 12-month adverse events using the lowest hsCRP group (<2.0 mg/L) as reference. The primary endpoint was MACCE, defined as the composite of all-cause death, myocardial infarction (MI), or stroke. Secondary endpoints were MACCE individual components, target vessel revascularization (TVR), stent thrombosis and bleeding. Results A total of 10,811 patients were included in the analysis. Of these, 6,210 (57.4%) had hsCRP <2.0 mg/L, 1,624 (15.0%) between 2 and 3 mg/L and 2,977 (27.6%) >3.0 mg/L. Incidence of anemia, diabetes mellitus, peripheral and cerebrovascular artery disease, atrial fibrillation and chronic kidney disease increased stepwise across hsCRP groups. Moreover, patients with higher hsCRP tended to present more frequently with unstable angina and higher baseline LDL cholesterol levels. As regards procedural variables, coronary artery disease severity and PCI complexity did not differ significantly across groups. When compared with patients with hsCRP < 2, hsCRP > 3 mg/L was associated with a greater adjusted risk of MACCE (4.9% vs 2.4%; HR 1.75 % CI 1.35 - 2.28), all-cause death (2.5% vs 0.9%, HR 2.34, 95%CI 1.57-3.47) and MI (2.5% vs 1.3%; HR 1.58 95%CI 1.11-2.26) (Figure 1). Risks of stroke, TVR, stent thrombosis and bleeding did not significantly differ across hsCRP groups (Table 1) Conclusions In patients undergoing PCI, elevated hsCRP values exceeding 3 mg/L exhibit a more robust association with the risk of MACCE and all-cause mortality, as compared with both hsCRP < 2.0 and between 2.0 and 3.0 mg/L. In this context, the use of hsCRP might improve the stratification of patients associated with higher inflammatory burden.

Burden of systemic inflammation and associated health outcomes in adults with atherosclerotic cardiovascular disease managed in routine care

Abstract Background The burden and outcomes of inflammation in people with atherosclerotic cardiovascular disease (ASCVD) are poorly defined, particularly beyond the controlled settings of trials and research cohorts. Methods We conducted a longitudinal observational study of adults with ASCVD undergoing C-reactive-protein (CRP) testing in routine healthcare in Stockholm, Sweden. After excluding CRP tests associated with acute illness and patients with medications/conditions that bias CRP interpretation, the systemic inflammation of participants was defined over a 3-month ascertainment window. Baseline determinants of CRP≥2 mg/L were explored with logistic regression, and baseline CRP categories were compared via Poisson and Cox regression for subsequent healthcare resource utilization and occurrence of major adverse cardiovascular events (MACE), heart failure hospitalization, and all-cause death. Result After applying inclusion/exclusion criteria, we identified 84,399 adults with ASCVD with a mean age of 71 years and of which 54% were men. In total, 60% had CRP≥2 mg/L. At baseline, female sex, older age, lower kidney function, albuminuria, diabetes, hypertension, and recent anemia, were associated with CRP≥2 mg/L. Conversely, the use of RASi, antiplatelets, and lipid-lowering therapy were associated with lower odds. Over a median follow-up of 6.4 years and compared to people with CRP <2 mg/L, those with CRP≥2 mg/L had a higher rate of hospitalizations, days spent in hospital, outpatient consultations, and dispensed medications during follow-up (P<0.05 for all). They also had a higher rate of MACE [adjusted hazard ratio (HR), 1.30; 95% CI, 1.27–1.33], heart failure hospitalization [1.24; 1.20–1.39], and all-cause death [1.35; 1.20–1.30]. Results were consistent across subgroups and more granular CRP categories, and robust to the exclusion of extreme CRP values or early events. Conclusions Two in three adults with ASCVD have systemic inflammation. A CRP≥2 mg/L is associated with excess healthcare resource utilization as well as increased rates of MACE, heart failure, and death.

Measuring only sitting blood pressure without considering supine blood pressure underestimates cardiovascular risk in the elderly

Abstract Background and Objective Elderly individuals exhibit greater variability in blood pressure (BP) readings between sitting and supine positions. Nocturnal hypertension (supine position) is closely associated with cardiovascular diseases and mortality. However, the relationship between supine BP and cardiovascular risk remains unclear. This study aims to investigate the association between the occurrence of major adverse cardiovascular events (MACEs) with BP in sitting and supine positions. Methodologies A total of 3363 participants aged 65 years or older from the Northern Shanghai Study were included. Each participant is given 3 consecutive sitting SBP readings (SBP1, SBP2, SBP3) at 2-minute intervals, we then calculated the SBP1-2 (average of SBP1 and SBP2), SBP2-3 (average of SBP2 and SBP3), SBP1-2-3 (average of SBP1, SBP2 and SBP3). we also collected two supine BP readings (S-SBP1, S-SBP2). Kaplan-Meier and Cox proportional hazard regression were used to investigate the association of sitting and supine BP with MACEs (composite of nonfatal myocardial infarction, nonfatal stroke, or death). Results The mean age of participants was 71.5 years, and 1467(43.6%) were men. After a median of 6.4-year follow-up, a total of 362 events were recorded. Among 3 successive BP readings, SBP2-3 had strongest association with MACEs incidence (hazard ratio, 1.12 [1.00-1.26] per SD). Multiple cox proportional hazard regression showed supine BP had significant value in predicting MACEs, acute myocardial infarction (AMI) and mortality compared to sitting BP. Kaplan-Meier revealed significant differences in MACEs rates among participants without hypertension (HTN) in both sitting and supine positions, with HTN in both positions, or those with HTN in either position (Log rank P < 0.01). Compared to participants without HTN in both sitting and supine positions, those with HTN in both positions had a 1.4-fold (hazard ratio,1.40[1.08-1.82]) higher risk of MACEs and 2-fold (hazard ratio,2.01[1.24-3.26]) higher risk of stroke. Conclusion Supine BP measurements are more valuable than sitting BP in predicting MACEs in elderly individuals. Hypertension in both positions significantly increases the risk of MACEs. Taken together, supine BP may also need to be emphasized in the elderly.central illustration

HIV and cardiovascular risk: should we use other targets for cholesterol control? Brazilian data compared to major studies

Abstract In daily clinical practice, cardiologists are confronted with patients with HIV/AIDS and this population needs special attention due to their higher cardiovascular risk. Studies show an increase in cardiovascular disease (CVD) among people with HIV/AIDS and one of the main causes of death in this group. HIV is associated with dyslipidaemia and endothelial damage, which have been proposed as a cause of the increased risk of events, and HIV replication is a determining factor in endothelial dysfunction. With antiretroviral therapy (ART) there has been a reduction in morbidity and mortality from HIV/AIDS, however, several studies have shown an increase risk factors for CVD in this population, both in individuals on ART and those not on it. Two high-impact studies related to cardiovascular risk in the HIV population are Start and Smart. Studies are important for understanding this occurrence and its relationship with the presence of the virus and the use of antiretroviral therapy in this population. In view of the higher cardiovascular risk of these patients and the question of whether they deserve a different cholesterol target from other populations. Methods A retrospective, observational study was carried out on a sample of HIV patients from the Brazilian STD/AIDS Reference Centre (CRT), selected by lottery using their registration number, from 1 January 2011 to February 2023, aged over 18. 148 medical records were assessed and the following were collected population characteristics. Discussion: the CRT data were compared with the Start and Smart studies. The Reprieve study showed benefits earlier than expected with patients receiving a statin. An interim analysis revealed a 35 per cent reduction in serious adverse cardiovascular events in the statin group, leading to the placebo group stopping earlier. The viral load varied between the studies, with CRT having an average of 500,000 copies/ml, Start 12,759 copies/ml and Smart less than 400 copies/ml. Studies have associated HIV infection and higher viral loads with impaired endothelial function and vasodilation. Despite the data in the literature, all the patients with heart disease had undetected viral loads and CD4+ cell counts above 500 cells/mm³. Those with a high viral load in the study were not the ones with CVD. Conclusions In CRT, the percentage of primary events attributable to serious conditions unrelated to AIDS was 1.3 per cent. Analysing biomarkers could elucidate the effects of antiretroviral therapy on arterial disease. Another fact that probably justifies the low occurrence of cardiovascular and cerebral events in CRT is the multidisciplinary care given to patients, providing intensive primary and secondary prevention through counselling and follow-up. We suggest better control of cardiovascular risk factors with multi-professional intervention and more aggressive targets for the control of comorbidities.Characteristics and Cardiovascular risk

A practical risk model based on Lasso-Cox regression for angina with nonobstructive coronary arteries (ANOCA) patients

Abstract Background Coronary flow reserve (CFR) reduction is currently one of the main criteria for risk-stratifying patients with angina and nonobstructive coronary artery disease (ANOCA). However, CFR depends on resting and vasodilated coronary hemodynamics, and a theoretical concern remains that physiological changes may inadvertently affect the result. Purpose We aim to fit different risk models for patients with ANOCA, which further provides applicable guidance to clinical doctors for their patients. Methods Between May 2018 and October 2023, 251 consecutive patients who were diagnosed as ANOCA were enrolled from Qilu Hospital of Shandong University, and the median follow-up was 800 (493, 1221) days. Demographic characteristics, cardiovascular risk factors, cardiac structure and function index, echocardiography-derived coronary flow velocity, coronary flow velocity-time integral, and CFR were collected. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regression analyses were used to screen for significant parameters that were included to develop a novel predictive nomogram model. Receiver operating characteristic curve and calibration curve were used to evaluate the performance and clinical utility of the nomogram. Results In LASSO regression selection, five variables, diabetes, global work efficiency (GWE), global wasted work (GWW), decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 (Figure 1) showed their correlation to the occurrence of major adverse cardiovascular events (MACE). Univariate Cox regression analysis shows that diabetes (hazard ratio [HR] = 4.108; 95% confidence interval [CI], 2.296–7.350; p = 0.001), GWE (HR = 0.890; 95% CI, 0.856–0.926; p = 0.001), GWW (HR = 1.005; 95% CI, 1.004–1.007; p = 0.012), decreased hyperemic coronary flow velocity (HR =3.405; 95% CI, 1.730–6.702; p = 0.001) and peak flow velocity-derived CFR<2.5 (HR =3.456; 95% CI, 1.898–6.292; p = 0.001) were predictors of recurrent chest pain. Multivariate analysis showed that the association of diabetes (HR = 2.735; 95% CI, 1.452–5.152; p = 0.002), GWW (HR = 1.004; 95% CI, 1.001–1.007; p = 0.010), and peak flow velocity-derived CFR<2.5 (HR = 2.650; 95% CI, 1.306–5.380; p = 0.007) with MACE remained statistically significant after adjusting for other variables. A nomogram incorporated the predictors mentioned above; it is presented in Fig.2. Internal validation showed that the model has good predictive performance. The areas under the curve (AUCs) for prediction of the risk of MACE was 0.849 (Fig.3). The calibration curve for predicting chest pain recurrence shows a good agreement between prediction and observation (Fig.4). Conclusions Diabetes, GWE, GWW, decreased hyperemic coronary flow velocity (<0.63m/s), and peak flow velocity-derived CFR<2.5 are significant in identifying the occurrence risk of MACE for ANOCA patients.

Safety and efficacy of aspiration thrombectomy with intracoronary tirofiban VS aspiration thrombectomy alone in patients undergoing primary PCI: a systematic review and meta-analysis

Abstract Background Primary percutaneous coronary intervention (PPCI) may be complicated by intracoronary thrombus accumulation in ST elevation myocardial infarction (STEMI) leading to decrease in myocardial perfusion and increase in infarct size. The utilization of aspiration thrombectomy and intracoronary tirofiban in STEMI patients undergoing PPCI hold clinical relevance by removal of thrombus burden, potentially reducing distal embolization and improving myocardial perfusion and by targeting platelet aggregation to mitigate thrombotic complications, respectively. Given the paramount importance of achieving rapid and effective reperfusion in STEMI, the evaluation of these interventions is warranted to assess overall impact on patient outcomes in terms of safety and efficacy. Purpose The current meta-analysis aims to investigate the clinical outcomes of aspiration thrombectomy (AT) with intracoronary tirofiban versus AT alone during PPCI. Methods A systematic search for randomized controlled trials that evaluate the safety and efficacy of aspiration thrombectomy with intracoronary tirofiban in STEMI patients who underwent PPCI was done using PubMed, MEDLINE, Embase, Cochrane, Clinicaltrials.gov. and Herdin PH. Studies included those between 2010 - 2023 and involved human subjects. Search terms included "Aspiration Thrombectomy", "Intracoronary Tirofiban", "Primary Percutaneous Coronary Intervention" and "STEMI patients". Results Four RCTs (n: 490 participants) were included in this meta-analysis comparing aspiration thrombectomy with intracoronary tirofiban versus aspiration thrombectomy alone in STEMI patients undergoing PPCI. The results revealed no statistically significant difference in ST segment resolution (RR 1.02, 95%, CI: 0.97 - 1.08, P = 0.41, I2 = 0%), myocardial blush grade 2-3, (risk ratio of 1.04, 95%, CI: 0.97 – 1.12, P = 0.22, I2 = 62%) and TIMI 3 flow (risk ratio of 1.0, 95% CI: 0.95 - 1.04, P = 0.87). The occurrence of major adverse cardiovascular events did not significantly differ between the two groups (RR 0.46, 95% CI: 0.19 – 1.09, P = 0.08, I2 = 0%). There was no statistically significant difference in terms of bleeding when combining intracoronary tirofiban to standard medical therapy (RR 1.35, 95% CI: 0.64 – 2.84, P= 0.78, 4 trials [490 patients]). Conclusion In primary percutaneous coronary intervention, MACE outcomes of aspiration thrombectomy with intracoronary tirofiban were similar to that for aspiration thrombectomy alone in terms of improving myocardial perfusion in STEMI patients without increasing the risk for bleeding. Our meta-analysis suggests that AT alone may be the more acceptable standard during PPCI when encountering heavy thrombus burden. Future validated studies may help further investigate the strategy of adding tirofiban during aspiration thrombectomy.1. Primary Outcomes2. Secondary Outcomes

Triggers of type 2 myocardial infarction: implications for long-term prognosis

Abstract Background Type 2 myocardial infarction (T2MI) is characterized by a mismatch between myocardial oxygen supply and demand, unrelated to acute coronary thrombosis. This discrepancy arises from triggers, which may or may not be of cardiac origin. Common cardiac triggers include coronary artery spasm, coronary embolism, and arrhythmias, whereas non-cardiac triggers encompass factors such as anemia, hypertension/hypotension, sepsis, renal damage, and respiratory failure. However, identifying these triggers isn't always straightforward. Aim Our study aimed to identify, whenever possible, the triggers contributing to the oxygen supply-demand mismatch in T2MI cases, as defined by the Fourth Universal Definition of Myocardial Infarction. Additionally, we sought to explore the correlation between these triggers and patient prognosis. Methods We enrolled all consecutive patients diagnosed with non-ST-segment elevation myocardial infarction (NSTEMI) who met the criteria for T2MI and underwent coronary angiography within 72 hours of diagnosis. Patients were categorized into three groups based on the trigger causing T2MI: cardiac, non-cardiac, and unidentified. The primary endpoint was the occurrence of major adverse cardiovascular events (MACEs), including all-cause mortality, new myocardial infarction, hospitalization for heart failure, and ischemic stroke, during long-term follow-up. We estimated MACE-free survival using Kaplan-Meier curves and compared it among the three groups using the log-rank test. Multivariable logistic regression analysis was performed to identify independent predictors of MACE. Results The final cohort comprised 598 T2MI patients, with 308 having a cardiac trigger, 147 having a non-cardiac trigger, and 143 with an unidentified trigger. The mean age of the overall population was 69.6±13.1 years, with a median follow-up time of 25 (13-49) months. Kaplan-Meier curves demonstrated statistically significant differences in MACEs based on the trigger causing T2MI (p<0.001). Specifically, patients with an unidentified trigger exhibited a better prognosis, while those with a non-cardiac trigger had a worse prognosis during long-term follow-up. Multivariable logistic regression analysis confirmed that not having an identified trigger is an independent protective factor for MACEs (HR 0.63, 95% CI 0.45-0.89, p=0.009, unidentified trigger vs cardiac + non-cardiac trigger). Conclusions T2MI is prevalent in clinical practice, yet reliable outcome predictors remain elusive. Our findings indicate a relationship between the type of trigger precipitating T2MI and patient prognosis, notably demonstrating that the absence of a specific identifiable trigger is linked to a more favorable long-term outcome. Further studies are needed to better define the prognostic stratification of these patients.MACE-free survival Kaplan Meier

Relationship between changes in renal function after acute phase of tafamidis administration and left ventricular diastolic function at mid-term follow-up in transthyretin cardiac amyloidosis

Abstract Background A large number of heart failure (HF) patients present with various degrees of renal dysfunction, known as cardio-renal syndrome. Renal impairment in HF patients is also associated with an independent risk factor for morbidity and mortality. Transthyretin (TTR) amyloidosis (ATTR) is characterized by disintegrated liver-derived TTR that accumulates as amyloid fibrils in the myocardium, leading to initially presenting as left ventricular (LV) hypertrophy and LV diastolic dysfunction. Although there is no proven therapy for patients with ATTR cardiomyopathy (ATTR-CM), tafamidis meglumine, a TTR stabilizer, has been associated with favorable outcomes. Although the kidneys are also an important organ where amyloid deposition occurs, the effect of tafamidis on renal function and its relationship to LV diastolic function is unclear. Purpose The purpose of this study was to investigate the relationship between changes in renal function after the acute phase of tafamidis administration and LV diastolic function at mid-term follow-up in patients with ATTR-CM. Methods We studied 56 patients with biopsy-proven ATTR-CM who were treated with tafamidis. All patients underwent blood examinations before and 45.6 ± 23.0 days after the acute phase of tafamidis administration. Echocardiography was performed before and 15.6 ± 9.8 months after the mid-term of tafamidis administration. The primary endpoint was defined as a composite of cardiovascular death or HF hospitalization for 5.0 years. Results Twelve patients had improved renal function as assessed by estimated glomerular filtration rate in the acute phase after tafamidis administration, while 44 patients deteriorated. In the group with improved renal function in the acute phase after tafamidis administration, pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E’) and left atrial volume index (LAVI) tended to improve at mid-term follow-up compared to the non-improved group. (E’: 0.8 ± 1.7 cm/s vs. 0.2 ± 1.1 cm/s, p=0.127, LAVI: -8.7 ± 12.0 mL/m2 vs. 0.2 ± 16.8 mL/m2, p=0.093). Furthermore, Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with improved renal function in the acute phase after tafamidis administration tended to be lower than those without (log-rank P=0.137). Conclusions The improvement of renal function in the acute phase after tafamidis administration was associated with the improvement of LV diastolic function at mid-term follow-up, leading to favorable outcome. Our findings may provide new insights for the management of patients with ATTR-CM.

Low density lipoprotein cholesterol and cardiovascular disease risk in patients with absence of coronary artery calcification: a multicenter cohort study

Abstract Background Low-density lipoprotein cholesterol (LDL-C) plays a central role in the development of coronary heart disease (CHD). Absence of coronary artery calcification (CAC 0), as assessed by coronary computed tomography angiography (CCTA), is associated with a favorable outcome as it indicates a low burden of atherosclerosis. However, questions remain regarding the risk of non-calcified plaque and CHD in younger patients with CAC zero, as atherosclerosis tends to be non-calcified in earlier stages. Purpose To assess if LDL-C is associated with presence of non-calcified plaque and future cardiovascular events in patients with CAC zero across the age spectrum. Methods This observational multicenter cohort study included patients aged 18 years or more who underwent CCTA between January 2008 and May 2021 with CAC zero. LDL-C was measured prior to CCTA. Patients were followed from date of CCTA to occurrence of cardiovascular event, death, or 1st of October 2022. No patients were lost to follow-up. We assessed the association between LDL-C and presence of non-calcified plaque on CCTA as adjusted odds ratios, and risk for myocardial infarction and CHD (myocardial infarction or coronary revascularization) as adjusted hazard ratios using Cox regression analyses, across different age groups. Results A total of 23,776 patients with CAC zero were included in the study. Median age was 54 years (IQR 47-61) and 14,605 (61%) were women. During median follow-up of 5.5 years, 165 (0.7%) and 427 (1.8%) experienced myocardial infarction and CHD, respectively. Overall, the prevalence of non-calcified plaque was 11.1% (n=2,650). Higher LDL-C was associated with presence of non-calcified plaque with an odds ratio of 1.21 (95% CI 1.16-1.27) per 1 mmol/L higher LDL-C. Individuals aged ≤45 years had a higher odds ratio for non-calcified plaque per 1 mmol/L higher LDL-C compared to individuals aged 46-60 and >60 years; 1.36 (95% CI 1.22-1.52), 1.22 (95% CI 1.15-1.30) and 1.13 (95% CI 1.04-1.22), respectively, p value for interaction between the youngest and oldest age group was <0.05. Overall, LDL-C was associated with higher risk for myocardial infarction and CHD with hazard ratios of 1.29 (95% CI 1.10-1.52) and 1.26 (95% CI 1.14-1.39) per 1 mmol/L higher LDL-C, despite CAC zero. Conclusions Particularly in younger patients with absence of CAC, elevated LDL-C is associated with presence of non-calcified plaque and increased risk for future cardiovascular events. These data are important for clinical practice, as they demonstrate the importance of managing LDL-C in younger individuals over the long-time horizon despite CAC zero.

The knowledge, attitude and practice of cardiologists versus other specialists about the safety and efficacy of influenza vaccination in patients with cardiovascular diseases

Abstract Background Influenza vaccination has been shown to reduce the occurrence of cardiovascular events, both in the general population and especially in individuals with cardiovascular disease. However, the extent to which cardiologists and other physicians support and prescribe influenza vaccination for patients with cardiovascular diseases is not known. Purpose To explore cardiologists' and other specialists' opinions on the safety and efficacy of influenza vaccination in preventing cardiovascular events. Methods From September 2023 to February 2024, a survey was conducted among physicians of any specialty, following the Checklist for Reporting Results of Internet E-Surveys (CHERRIES). The survey was available in 5 languages. Participants' opinions were assessed using Likert-type scales. Non-probabilistic convenience sampling was employed, and duplicated responses were prevented using the SurveyMonkey® platform that identifies duplicated IP addresses. Results A total of 2550 physicians from 44 countries answered the survey; the mean age was 46.1±13.1 years, 46.4% were women, and 17.1% were in training. Among respondents 43.6% were cardiologists. While 91.8% of participants considered the influenza vaccine to be very safe, and 90.6% believed that adverse effects of this intervention were rare, a significant proportion did not consider Influenza vaccine to be very beneficial in reducing acute myocardial infarction (54.4% for cardiologists vs 59.3% for other specialists, p=0.013) or stroke (62.2% for cardiologists vs 64.9% for other specialists, p=0.167). summarizes the participants’ opinions regarding the benefits and risks of influenza vaccination. Regarding potential barriers to achieving higher vaccination rates among patients with cardiovascular disease, cardiologists' opinions were similar to those of other specialists (Table 2). Patient beliefs and patients’ fear of vaccine-related adverse effects were identified as major barriers by both cardiologists and other specialists. Only 19.0% of participants reported having some type of checklist system to remind them to recommend the vaccine to their patients. While 73.0% of participants found this topic highly relevant to their daily clinical practice, with no differences between groups (p=0.178), a notable proportion, comprising 48.5% of cardiologists and 47.1% of other specialists, expressed the necessity for additional training to address the risk-benefit ratio of influenza vaccination with their patients (p=0.485). Conclusion Our data suggest that cardiologists and other specialists view the influenza vaccine as safe with a low rate of adverse effects, both in the general population and in individuals with cardiovascular disease. However, a significant proportion of them are unaware of the vaccination's benefit in reducing cardiovascular events. Additionally, about half of the surveyed professionals expressed a need for further education to discuss the benefits of vaccination with their patients.

Effect of tafamidis on left atrial function in patients with transthyretin amyloid cardiomyopathy

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is characterized by the functional and structural consequences of amyloid infiltration predominantly within the ventricles, causing biventricular wall thickening. Amyloid infiltration can be observed in left atrium in ATTR-CM, however, the association of left atrial (LA) myocardial function with cardiovascular events and changes in LA myocardial function with tafamidis administration have not been elucidated. Purpose The aim of this study was to identify the association between baseline LA reservoir function evaluated by left atrial reservoir strain and cardiovascular events. Furthermore, monitoring the LA reservoir function before and after tafamidis administration, we also investigated the baseline factors associated with changes in LA reservoir function in patients with ATTR-CM. Methods We studied 55 patients with biopsy-proven ATTR-CM who were started on tafamidis in our institution between July 2019 and December 2022 (age: 76 ± 2 years, male: 93%). The primary endpoint was defined as hospitalization for heart failure or cardiovascular death during a median follow-up period of 28 ± 4 months after tafamidis administration. Furthermore, we assessed the factors associated with changes in LA function before and 25 ± 3 months after tafamidis administration for 49 patients who underwent sufficient follow-up echocardiography. Results During the follow-up period, 8 patients had cardiovascular death or cardiovascular hospitalization. The Kaplan-Meier curve indicated that the occurrence of cardiovascular events for patients with LA strain ≥ the median 8.6% was significantly lower than for those with LA strain < 8.6% (log-rank P =0.002; Figure A). Furthermore, comparing LA strain before and after tafamidis administration, the group with worsening LA strain tended to be older (79.0 ± 2.0 years vs. 73.6 ± 3.3 years, P=0.004), have higher brain natriuretic peptide (350 ± 83 pg/mL vs. 199 ± 47 pg/mL, P=0.003), have lower global longitudinal strain (GLS) (9.8 ± 1.4 % vs. 12.6 ± 1.6 pg/mL, P=0.008), and higher relative apical longitudinal strain index (1.63 ± 0.4 % vs. 1.14 ± 0.2 %, P=0.021). The multivariate logistic regression analysis was that age, GLS and relative apical longitudinal strain index were the independent determinants for deterioration of LA strain after tafamidis administration (Figure B). Conclusion In our study, baseline LA reservoir function was found to be closely associated with cardiovascular events after tafamidis administration, while age, GLS and relative apical longitudinal strain index were associated with worsening LA strain after tafamidis administration. Our findings could represent an additional parameter for the effective management of patients with ATTR-CM.Figure AFigure B

Is genetic information helpful in predicting recurrent events in young patients after acute coronary syndrome?

Abstract Coronary Artery Disease (CAD) shares environmental and genetic factors. Young patients with acute coronary syndrome (ACS) carry a poor long-term prognosis. The clinical utility of genetic information in predicting CAD events remains unknown. Aim Evaluate the clinical utility of a multiplicative Genetic Risk Score (mGRS) to predict lifelong residual risk in CAD patients below 55 years with few risk factors. Methods 475 non-diabetic patients with LDL cholesterol levels below 100mg/dL at the first admission who suffered a prior MI at age ≤55 years were followed prospectively for a mean of 5.6±5.3 years. A mGRS was performed with nine variants associated with CAD but not with traditional risk factors (TRF): CDKN2B-AS1 (rs1333049 and rs4977574), TCF21 (rs12190287), PHACTR1 (rs1332844), MIA3 (rs17465637), ADAMTS7 (rs3825807), ZC3HC1 (rs11556924), SMAD3 (rs17228212) and GJA4 (rs618675). The mGRS was subdivided into terciles. Using Cox regression analysis, the predictive and discriminative score ability for events was evaluated. C-statistic discriminated cardiovascular events occurrence. Whether mGRS was included in the TRF model, Net Reclassification Improvement (NRI), or Integrated Discrimination Improvement (IDI) reclassified patients. Kaplan-Meier method estimated survival curves. Results There were 153 patients with at least one cardiovascular event. The bivariate analysis showed the strongest correlation with second and third mGRS tercile, multivessel disease, left ventricular dysfunction, and inflammation. Multivariate Cox regression HR adjusted for events was 1.44 (p=0.103) for the intermediate and 2.00 (p=0.001) for the high-risk tercile. The mGRS inclusion improved C-statistic (∆C-index=0.010; p=0.004), NRI (35.4%; p<0.0001) and IDI (2.7%; p=0.0005). Conclusions Our 9-SNP mGRS better identified and reclassified younger CAD patients with a high probability of cardiovascular events, improving clinical decision-making and reducing costs for therapeutic strategies.

Vital Predictive and Prognostic Roles of Triglyceride-Glucose Index in Women With Acute Myocardial Infarction: A Retrospective Cohort Study.

As a biomarker of insulin resistance (IR) in patients with acute myocardial infarction (AMI), the triglyceride-glucose index (TyG index) has received significant attention. However, most research on AMI has focused on male patients, as it is traditionally believed to primarily affect males. Therefore, this study was conducted on a female population with AMI to investigate the potential correlation between the TyG index and their outcomes. A total of 320 women who were admitted to Fujian Provincial Hospital for AMI between January 2017 and December 2019 were included in this study. The TyG index was calculated using the following formula: ln [fasting triglycerides (TG) (mg/dL) × fasting plasma glucose (FPG) (mg/dL)/2]. The primary endpoint of the study was the occurrence of major adverse cardiovascular and cerebrovascular events (MACCEs), which included all-cause mortality, myocardial infarction, repeat revascularization, rehospitalization for heart failure and stroke. The association between the TyG index and unfavorable outcomes in female patients was investigated using the Cox proportional hazards regression model. It was ultimately estimated that 111 patients developed MACCEs. Females with high TyG indices had a higher prevalence of diabetes, elevated heart rates, and hemoglobin A1c, as well as a higher likelihood of undergoing thrombus aspiration and stent placement. The TyG index was found to be positively correlated with the prevalence of hypertension, diabetes, low-density lipoprotein cholesterol, hemoglobin A1c, and damaged vessels. However, this correlation was modest, yet statistically significant. Furthermore, after adjusting for conventional risk factors, the TyG index (HR: 4.292, 95% CI: 2.784-6.616, p < 0.001) was independently associated with MACCEs. As an independent risk predictor, the TyG index has the potential to enhance clinical outcomes for women with AMI.

The role of hemoglobin A1c as a predictor of major adverse cardiovascular events in patients with type 2 diabetes mellitus after percutaneous coronary intervention: a case-cohort study

BackgroundFew studies have investigated the potential predictive value of glycosylated hemoglobin A (HbA1c) and clinical outcomes in diabetic patients after percutaneous coronary intervention (PCI), and the results of the reports have often been inconclusive and contradictory. We have organized a study to investigate the relationship between HbA1c and the occurrence of major adverse cardiovascular events (MACE) in diabetic patients after PCI.MethodsThis case-cohort study was conducted on 563 diabetic patients who underwent PCI. All studied patients had an HbA1c level measured within 24 h before angioplasty. All patients were followed for six months regarding the occurrence of MACE, and the HbA1c level was measured again at the end of the sixth month of follow-up. In the case of MACE, the subjects were considered the case group, and other non-MACE patients were included in the control group.Results505 patients remained in the study at the end of follow-up. MACE occurred in 23 (4.6%) patients during the first month and in 57 (11.3%) patients by the end of the sixth month. Baseline HbA1c was an independent predictor of MACE and mortality at the end of month-6 (P = 0.008 and 0.001, respectively).ConclusionsThe level of HbA1c at the time of admission has a significant predictive value for the occurrence of MACE in diabetic patients who undergo PCI. However, post-PCI glycemic control may not effectively reduce the risk of MACE in this population.Clinical trial registrationNot applicable.

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

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