Is systemic inflammation a missing link between cardiometabolic index with mortality? Evidence from a large population-based study.

BACKGROUND: This study sought to elucidate the associations of cardiometabolic index (CMI), as a metabolism-related index, with all-cause and cardiovascular mortality among the older population. Utilizing data from the National Health and Nutrition Examination Survey (NHANES), we further explored the potential mediating effect of inflammation within these associations. METHODS: A cohort of 3029 participants aged over 65 years old, spanning six NHANES cycles from 2005 to 2016, was enrolled and assessed. The primary endpoints of the study included all-cause mortality and cardiovascular mortality utilizing data from National Center for Health Statistics (NCHS). Cox regression model and subgroup analysis were conducted to assess the associations of CMI with all-cause and cardiovascular mortality. The mediating effect of inflammation-related indicators including leukocyte, neutrophil, lymphocyte, systemic immune-inflammation index (SII), neutrophil to lymphocyte ratio (NLR) were evaluated to investigate the potential mechanism of the associations between CMI and mortality through mediation package in R 4.2.2. RESULTS: The mean CMI among the enrolled participants was 0.74±0.66, with an average age of 73.28±5.50 years. After an average follow-up period of 89.20 months, there were 1,015 instances of all-cause deaths and 348 cardiovascular deaths documented. In the multivariable-adjusted model, CMI was positively related to all-cause mortality (Hazard Ratio (HR)=1.11, 95% CI=1.01-1.21). Mediation analysis indicated that leukocytes and neutrophils mediated 6.6% and 13.9% of the association of CMI with all-cause mortality. CONCLUSION: Elevated CMI is positively associated with all-cause mortality in the older adults. The association appeared to be partially mediated through inflammatory pathways, indicating that CMI may serve as a valuable indicator for poor prognosis among the older population.

Triglyceride-glucose index is associated with myocardial ischemia and poor prognosis in patients with ischemia and no obstructive coronary artery disease.

BACKGROUND: Ischemia and no obstructive coronary artery disease (INOCA) is increasingly recognized and associated with poor outcomes. The triglyceride-glucose (TyG) index is a reliable alternative measure of insulin resistance significantly linked to cardiovascular disease and adverse prognosis. We investigated the association between the TyG index and myocardial ischemia and the prognosis in INOCA patients. METHODS: INOCA patients who underwent both coronary angiography and myocardial perfusion imaging (MPI) were included consecutively. All participants were divided into three groups according to TyG tertiles (T1, T2, and T3). Abnormal MPI for myocardial ischemia in individual coronary territories was defined as summed stress score (SSS) ≥ 4 and summed difference score (SDS) ≥ 2. SSS refers to the sum of all defects in the stress images, and SDS is the difference of the sum of all defects between the rest images and stress images. All patients were followed up for major adverse cardiac events (MACE). RESULTS: Among 332 INOCA patients, 113 (34.0%) had abnormal MPI. Patients with higher TyG index had a higher rate of abnormal MPI (25.5% vs. 32.4% vs. 44.1%; p = 0.012). Multivariate logistic analysis showed that a high TyG index was significantly correlated with abnormal MPI in INOCA patients (OR, 1.901; 95% CI, 1.045-3.458; P = 0.035). During the median 35 months of follow-up, 83 (25%) MACE were recorded, and a higher incidence of MACE was observed in the T3 group (T3 vs. T2 vs. T1: 36.9% vs. 21.6% vs. 16.4%, respectively; p = 0.001). In multivariate Cox regression analysis, the T3 group was significantly associated with the risk of MACE compared to the T1 group (HR, 2.338; 95% CI 1.253-4.364, P = 0.008). CONCLUSION: This study indicates for the first time that the TyG index is significantly associated with myocardial ischemia and poor prognosis among INOCA patients.

Stress hyperglycemia ratio as a prognostic indicator for long-term adverse outcomes in heart failure with preserved ejection fraction.

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.

Prognostic impact of coronary microvascular dysfunction in patients with atrial fibrillation.

BACKGROUND: Coronary microvascular dysfunction (CMD) is frequently observed in atrial fibrillation (AF), the most commonly sustained arrhythmia. Nevertheless, an in-depth prognostic significance of CMD in AF is lacking. We aimed to provide insight into the predictive impact of CMD assessed by a novel non-invasive coronary angiography-derived index of microcirculatory resistance (caIMR) for major adverse events (MACE) in AF patients. METHOD: This study included patients with AF who underwent invasive coronary angiography due to suspected cardiac ischemia and did not exhibit obstructive epicardial coronary artery disease (≤50 % stenosis). The caIMR was prospectively evaluated, and the optimal cutoff value for predicting MACE was determined through ROC analysis. RESULT: A total of 463 patients with AF were enrolled. During a median of 33 months of follow-up, 111 (23.97 %) patients had MACE endpoints. The best caIMR cutoff value was 39.28. In patients with MACE, both the mean caIMR and the prevalence of elevated caIMR (caIMR>39.28) were significantly higher compared to those without MACE. An elevated caIMR was linked to a higher risk of MACE (log-rank P < 0.001) and emerged as an independent predictor of clinical outcomes (HR: 4.029; 95 % CI: 2.529-6.418; P < 0.001). In addition, the risk of MACE was higher in high caIMR patients with non-paroxysmal AF (log-rank P < 0.001) and no catheter ablation (log-rank P < 0.001). CONCLUSION: Elevated caIMR is common and showed a vital independent prognostic significance in AF patients. In addition to well-known risk factors, assessment of microvascular function can be a feasible approach for early prevention and a therapeutic target in AF patients.

Associations of cardiometabolic index with diabetic statuses and insulin resistance: the mediating role of inflammation-related indicators.

BACKGROUND: This study aimed to analyze the associations of cardiometabolic index (CMI) with diabetic statuses and insulin resistance (IR) using data from the National Health and Nutrition Examination Survey (NHANES) and examined the potential mediating role of inflammation in these correlations. METHODS: This study enrolled 9477 participants across four NHANES cycles from 2011 to 2018. The primary outcomes of the study included the risk of having prediabetes, diabetes and the level of the homeostasis model assessment of IR (HOMA-IR). Other outcomes including the levels of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) results, fasting insulin, the risk of oral hypoglycemic medicine use, insulin use, and retinopathy were also collected and analyzed. Logistic regression model, subgroup analysis, restricted cubic spine (RCS), and Pearson correlation coefficients were conducted to assess the associations of CMI with diabetic statuses and IR. The mediating role of inflammation was evaluated to investigate the potential mechanism of the associations between CMI and diabetic statuses. RESULTS: Among included participants, the CMI levels in normal participants, prediabetes and diabetes in this study were 0.48, 0.73 and 1.07. After multivariable adjustment, CMI was positively associated with the risk of prediabetes (OR = 1.49, 95% CI = 1.24-1.79), diabetes (OR = 2.14, 95% CI = 1.82-2.50) and the level of HOMA-IR (ß = 2.57, 95% CI = 2.14-3.01). Besides, an increased CMI was correlated with higher levels of FBG, HBA1c, OGTT results and fasting insulin as well as the greater risk of oral hypoglycemic medicine use and insulin use. The RCS showed an inverted L-shaped association of CMI with prediabetes and diabetes (P for non-linearity < 0.001). According to Pearson correlation coefficients, higher CMI was linked to higher rises in HOMA-IR (r = 0.224, P < 0.001). Inflammation-related indicators including leukocyte and neutrophil demonstrated significant mediating effects in the associations of CMI with prediabetes (15.5%, 9.8%), diabetes (5.1%, 6.0%) and HOMA-IR (3.3%, 2.6%). CONCLUSION: CMI was positively associated with the risk of worse diabetic statuses and higher level of IR while the associations may be partially mediated by inflammation-related indicators, suggesting that CMI could be a promising indicator for the prediction of severe diabetes and IR.

Association between the atherogenic index of plasma and adverse long-term prognosis in patients diagnosed with chronic coronary syndrome.

BACKGROUND: The Atherogenic Index of Plasma (AIP) is a newly identified biomarker associated with lipid metabolism, demonstrating significant prognostic capabilities in individuals diagnosed with cardiovascular disease. However, its impact within the context of chronic coronary syndromes (CCS) remains unexplored. Thus, the present investigation sought to examine the potential association between AIP levels and long-term clinical outcomes in patients diagnosed with CCS. METHODS: A total of 404 patients diagnosed with CCS and who underwent coronary angiography were included in this study. The AIP index was calculated as log (triglycerides / high-density lipoprotein-cholesterol). The patients were categorized into four groups based on their AIP values: Q1 (< -0.064), Q2 (-0.064 to 0.130), Q3 (0.130 to 0.328), and Q4 (> 0.328). The occurrence of major adverse cardiovascular events (MACE) was monitored during the follow-up period for all patients. Cox regression analysis and Kaplan-Meier curve analysis were employed to examine the relationship between AIP and MACE. Furthermore, ROC analysis was utilized to determine the optimal cut-off value of AIP for predicting clinical MACE. RESULTS: During the median 35 months of follow-up, a total of 88 patients experienced MACE. Notably, the group of patients with higher AIP values (Q4 group) exhibited a significantly higher incidence of MACE compared to those with lower AIP values (Q1, Q2, and Q3 groups) (31.7% vs. 16.8%, 15.7%, and 23.0% respectively; P = 0.023). The Kaplan-Meier curves illustrated those patients in the Q4 group had the highest risk of MACE relative to patients in the other groups (log-rank P = 0.014). Furthermore, the multivariate Cox regression analysis demonstrated that individuals in the Q4 group had a 7.892-fold increased risk of MACE compared to those in the Q1 group (adjusted HR, 7.892; 95% CI 1.818-34.269; P = 0.006). Additionally, the ROC curve analysis revealed an optimal AIP cut-off value of 0.24 for predicting clinical MACE in patients with CCS. CONCLUSION: Our data indicate, for the first time, that AIP is independently associated with poor long-term prognosis in patients suffering from CCS. The optimal AIP cut-off value for predicting clinical MACE among CCS patients was 0.24.

Association of stress hyperglycemia ratio and poor long-term prognosis in patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND: Stress hyperglycemia ratio (SHR) is a novel biomarker of true acute hyperglycemia condition and is associated with a worse prognosis in patients with myocardial infarction (MI). However, the effects of SHR in the setting of MI with non-obstructive coronary arteries (MINOCA) have not been investigated. This study aimed to explore the association between SHR and long-term clinical outcomes among MINOCA patients. METHODS: A total of 410 MINOCA patients were included in the final analysis of this study. The patients were divided into three groups based on the SHR tertiles: [SHR1 group (SHR ≤ 0.73), (n = 143); SHR2 group (SHR 0.73-0.84), n = 131; and SHR3 group (SHR ≥ 0.84), n = 136]. Follow-up for major adverse cardiovascular events (MACE) was conducted on all patients. Cox regression and Kaplan-Meier curve analysis were used to evaluate the relationship between SHR and MACE. The receiver operating curve (ROC) analysis was applied to obtain the optimal cut-off value of SHR for predicting clinical MACE. RESULTS: A total of 92 patients developed MACE during the mean 34 months of follow-up. A significant increase in MACE was observed in the SHR3 group compared to the SHR1 and SHR2 groups (35.3% vs. 15.4% and 16.8%, respectively; P < 0.001). The Kaplan-Meier curves demonstrate that SHR3 patients had the highest MACE risk compared to SHR1 and SHR2 patients (log-rank P < 0.001). In addition, when both SHR tertiles and diabetes status were considered, those with SHR3 and diabetes had the highest hazard of MACE (log-rank P < 0.001). Multivariate Cox regression analysis showed that the SHR3 is associated with a 2.465-fold increase in the risk of MACE (adjusted HR, 2.465; 95% CI 1.461-4.159, P = 0.001). The ROC curve analysis showed that the optimal SHR cut-off value for predicting clinical MACE among MINOCA was 0.86. CONCLUSION: Our data indicates, for the first time, that SHR is independently associated with poor long-term prognosis in patients suffering from MINOCA. The optimal SHR cut-off value for predicting clinical MACE among MINOCA patients was 0.86. These findings suggest that SHR may play a potential role in the cardiovascular risk stratification of the MINOCA population.

Association between the triglyceride-glucose index and the presence and prognosis of coronary microvascular dysfunction in patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is a strong determinant of prognosis in patients with chronic coronary syndrome (CCS). The triglyceride-glucose index (TyG index), an alternative method to evaluate insulin resistance, is positively correlated with the incidence and adverse outcomes of cardiovascular diseases. However, the relationship between the TyG index and the presence and prognosis of CMD in CCS patients has not been investigated. Therefore, we aimed to evaluate the association between the TyG index and the presence and clinical outcomes of CMD among CCS patients. METHODS: CCS patients who underwent coronary angiography between June 2015 to June 2019 were included. The TyG index was calculated as Ln[fasting triglycerides (mg/dL) × fasting blood glucose (mg/dL)/2]. Coronary angiography­derived index of microvascular resistance (caIMR) was used to measure microvascular function, and CMD was defined as caIMR ≥ 25U. Patients with CMD were divided into three groups (T1, T2, and T3 groups) according to TyG tertiles. The primary endpoint was major adverse cardiac event (MACE). RESULTS: Of 430 CCS patients, 221 patients had CMD. CMD patients had significantly higher TyG index than those without CMD. Sixty-three MACE was recorded during the follow-up duration among CMD patients, and the incidence rate of MACE was higher in the T3 group compared to T1/T2 groups (39.2% vs. 20.5% vs. 25.7%; P = 0.035). Multivariable logistic regression analysis showed that the TyG index was an independent predictor of CMD (OR, 1.436; 95% CI, 1.014-2.034; P = 0.042). Compared to the T1 group, the T3 group strongly correlated with the risk of MACE in CMD patients even after adjusting for additional confounding risk factors (HR, 2.132; 95%CI, 1.066-4.261; P = 0.032). CONCLUSION: TyG index is significantly associated with the risk of CMD, and it is an independent predictor of MACE among CMD patients with CCS. This study suggests that the TyG index has important clinical significance for the early prevention and risk stratification of CMD.

The prognostic value of CZT SPECT myocardial blood flow (MBF) quantification in patients with ischemia and no obstructive coronary artery disease (INOCA): a pilot study.

BACKGROUND: Despite the demonstrated adverse outcome, it is difficult to early identify the risks for patients with ischemia and no obstructive coronary artery disease (INOCA). We aimed to explore the prognostic potential of CZT SPECT in INOCA patients. METHODS: The study population consisted of a retrospective cohort of 118 INOCA patients, all of whom underwent CZT SPECT imaging and invasive coronary angiography (ICA). Dynamic data were reconstructed, and MBF was quantified using net retention model. Major adverse cardiovascular events (MACEs) were defined as cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, heart failure, late coronary revascularization, or hospitalization for unstable angina. RESULTS: During a median follow-up of 15 months (interquartile range (IQR) 11-20), 19 (16.1%) MACEs occurred; both stress myocardial blood flow (sMBF) ([Formula: see text]) and coronary flow reserve (CFR) ([Formula: see text]) were significantly lower in the MACE group. Optimal thresholds of sMBF<3.16 and CFR<2.52 were extracted from the ROC curves, and both impaired sMBF (HR: 15.08; 95% CI 2.95-77.07; [Formula: see text]) and CFR (HR: 6.51; 95% CI 1.43-29.65; [Formula: see text]) were identified as prognostic factors for MACEs. Only sMBF<3.16 (HR: 11.20; 95% CI 2.04-61.41; [Formula: see text]) remained a robust predictor when sMBF and CFR were integrated considered. Compared with CFR, sMBF provides better prognostic model discrimination and reclassification ability (C-index improvement = 0.06, [Formula: see text]; net reclassification improvement (NRI) = 0.19; integrated discrimination improvement (IDI) = 0.10). CONCLUSION: The preliminary results demonstrated that quantitative analysis on CZT SPECT provides prognostic value for INOCA patients, which may allow the stratification for early prevention and intervention.

Prognostic value of combined coronary angiography-derived IMR and myocardial perfusion imaging by CZT SPECT in INOCA.

BACKGROUND: A significant proportion of ischemia with non-obstructive coronary artery disease (INOCA) demonstrate coronary microvascular dysfunction (CMD), a condition associated with abnormal myocardial perfusion imaging (MPI) and adverse outcomes. Coronary angiography-derived index of microvascular resistance (caIMR) is a novel non-invasive technique to assess CMD. We aimed to investigate the prognostic value of combined caIMR and MPI by CZT SPECT in INOCA patients. METHODS: Consecutive 151 patients with chest pain and < 50% coronary stenosis who underwent coronary angiography and MPI within 3 months were enrolled. caIMR was calculated by computational pressure-flow dynamics. CMD was defined as caIMR ≥ 25. The endpoint was major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, angina-related rehospitalization, heart failure, and stroke). RESULTS: Of all INOCA patients, CMD was present in 93 (61.6%) patients. The prevalence of abnormal MPI was significantly higher in CMD compared with non-CMD patients (40.9% vs 13.8%, P < .001). CMD showed a higher risk of MACE than non-CMD patients. Patients with both CMD and abnormal MPI had the worst prognosis, followed by patients with CMD and normal MPI (log-rank P < .001). Cox regression analysis identified CMD (HR 3.121, 95%CI 1.221-7.974, P = .017) and MPI (HR 2.704, 95%CI 1.030-7.099, P = .043) as predictive of MACE. The prognostic value of INOCA patients enhanced significantly by adding CMD and MPI to the model with clinical risk factors (AUC = 0.777 vs 0.686, P = .030). CONCLUSION: caIMR-derived CMD is associated with increased risk of MACE among INOCA patients. Patients with abnormalities on both caIMR and MPI had the worse outcomes.

Screening and verifying the mutations in the LDLR and APOB genes in a Chinese family with familial hypercholesterolemia.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH. METHODS: Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed. RESULTS: WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother. CONCLUSIONS: The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.

Prognostic value of coronary microvascular dysfunction assessed by coronary angiography-derived index of microcirculatory resistance in diabetic patients with chronic coronary syndrome.

BACKGROUND: Coronary microvascular dysfunction (CMD) is common and is associated with unfavorable cardiovascular events in patients with diabetes mellitus (DM). Coronary angiography-derived index of microcirculatory resistance (caIMR) is a recently developed wire- and hyperemic agent-free method to assess CMD. We aimed to investigate the prognostic impact of CMD assessed by caIMR on clinical outcomes in patients with DM and chronic coronary syndrome (CCS). METHODS: CCS patients who underwent coronary angiography between June 2015 to May 2018 were included. Coronary microvascular function was measured by caIMR, and CMD was defined as caIMR ≥ 25U. The primary endpoint was major adverse cardiac events (MACE). Kaplan-Meier analysis and Cox proportional hazards models were used to assess the relationship between caIMR and the risk of MACE. RESULTS: Of 290 CCS patients, 102 patients had DM. Compared with non-diabetic patients, CMD (caIMR ≥ 25U) was higher among DM patients (57.8% vs. 38.3%; p = 0.001). During a mean 35 months follow-up, 40 MACE had occurred. Patients with caIMR ≥ 25 had a higher rate of MACE than patients with caIMR < 25 (20.6% vs. 8.2%, p = 0.002). Of these, the MACE rate was higher among DM patients with caIMR ≥ 25 than those with caIMR < 25 (33.9% vs. 14.0%; p = 0.022). In multivariable Cox analysis, caIMR ≥ 25 was independently associated with MACE in the DM patients but not in non-DM patients (HR, 2.760; 95% CI, 1.066-7.146; P = 0.036). CONCLUSION: CMD assessed by caIMR was common and is an independent predictor of MACE among diabetic patients with CCS. This finding potentially enables a triage of higher-risk patients to more intensive therapy.

Metabolic syndrome and the risk of adverse cardiovascular events in patients with myocardial infarction with non-obstructive coronary arteries.

BACKGROUND AND AIMS: Metabolic syndrome (MeS) is recognized as a significant predictor of poor outcomes in coronary artery disease. However, its prognostic implications in myocardial infarction with non-obstructive coronary arteries (MINOCA) have not been examined. We aimed at investigating the role of MeS on the clinical outcomes in MINOCA patients. METHODS AND RESULTS: Patients diagnosed with MINOCA between 2015 and 2019 were included. MeS was defined according to modified NCEP-ATPIII criteria. The primary endpoint was major adverse cardiovascular events (MACE). Cox regression analysis was used to evaluate the correlation between MeS and the hazard of MACE. The integrated discrimination improvement (IDI) and net reclassification index (NRI) were performed to assess MeS incremental predictive value. Of 281 MINOCA patients, 83 (29.5%) patients satisfied the MeS criteria. During a median follow-up duration of 28 months, MINOCA patients with MeS had a notably higher rate of MACE than those without MeS (30.1% vs. 17.6%, respectively P = 0.020). Cox regression analysis revealed that MeS was associated with an increased hazard of MACE (adjusted HR 2.126; 95% CI: 1.193-3.787, P = 0.010). When each component of MeS was analyzed as a categorized variable separately, only high fasting blood glucose and BMI ≥25 kg/m2 were associated with an increased hazard of MACE. Moreover, MeS had an incremental predictive ability for MACE when added to a model with clinical risk factors. CONCLUSION: MeS is relatively common in patients with MINOCA. The presence of MeS significantly increased the hazard of MACE among the MINOCA population.

Association between Initial Serum Total Bilirubin and Clinical Outcome in Myocardial Infarction with Non-Obstructive Coronary Arteries.

Background: Liver function parameters, particularly serum total bilirubin (TB), are closely associated with cardiovascular diseases. However, the impact of serum TB among patients with myocardial infarction and non-obstructive coronary (MINOCA) remains unknown. Our study investigated the relationship between serum TB at admission and long-term adverse clinical outcomes in MINOCA patients. Methods: A total of 273 consecutive MINOCA patients were categorized into low and high serum TB groups based on the optimal cut-off of 0.9 mg/dl. The primary endpoint was major adverse cardiovascular events (MACE), including cardiac death, non-fatal MI, heart failure, and angina rehospitalization. Receiver-operating characteristic, Cox regression, and Kaplan-Meier analyses were used to evaluate the association of high serum TB with cardiovascular outcomes. Results: High serum TB was found in 68 (24.9%) patients. The incidence of MACE was higher in the high TB group than in the low TB group after a median follow-up of 28 months (30.9 vs. 17.1%, P=0.015). The Kaplan-Meier curve analysis also indicated that patients in the high TB group had a higher risk of developing MACE (log-rank P=0.023). Cox regression analysis showed that high serum TB (>0.9mg/dl) significantly correlated with increased MACE risk (HR=1.90, 95%CI: 1.12-3.22, P=0.018). After adjusting for numerous clinical variables, the high serum TB remained significantly associated with an increased risk of MACE (HR=2.04, 95%CI: 1.05-3.94, P=0.034). Conclusion: High initial serum TB (>0.9mg/dl) is a robust predictor of poor clinical outcomes among MINOCA patients. In clinical settings, assessing serum TB at admission may help identify high-risk patients presenting with MINOCA.

Combination of White Blood Cell Count to Mean Platelet Volume Ratio and Neutrophil-to-Platelet Ratio Predicts Long-Term Adverse Events in Patients with MINOCA.

Background: White blood cell count to mean platelet volume ratio (WMR) and neutrophil-to-platelet ratio (NPR) have been demonstrated as prognostic inflammatory biomarkers of the acute coronary syndrome. We aimed to evaluate the prognostic value of WMR and NPR among myocardial infarction with nonobstructive coronary arteries (MINOCA) patients. Method: A total of 274 MINOCA patients were enrolled. Baseline clinical data, blood cell panel, and biochemical parameters were evaluated. The patients were classified according to the medians of WMR and NPR. The primary endpoint of the present study was major adverse cardiovascular events (MACE). Multivariable Cox regression analysis was used to assess the effect of independent variables of WMR and NPR on the dependent variable (MACE). Result: The median values of WMR and NPR were 701 and 0.03, respectively. During the median follow-up of 28 months, a total of 58 incidences of MACE occurred. The MACE rate was more frequent in high WMR and high NPR patients. In Kaplan-Meier analysis, the incidence of MACE was higher in WMR>701 and NPR>0.03 (long-rank P = 0.004 and P = 0.002, respectively). The combined high WMR and high NPR showed a significantly higher rate of MACE (long-rank P = 0.001). Cox regression analysis showed that the combined high WMR and high NPR were independent predictors of long-term MACE with the highest hazard ratio (HR, 2.511; 95% CI, 1.271 to 4.960; P = 0.008). Conclusion: High WMR and NPR separately or in combination were correlated with increased risk of MACE among MINOCA patients, suggesting WMR and NPR may assist as a reliable inflammatory marker in risk prediction of MINOCA patients.

Prognostic value of myocardial perfusion imaging with D-SPECT camera in patients with ischemia and no obstructive coronary artery disease (INOCA).

BACKGROUND: Myocardial perfusion imaging (MPI) with a novel D-SPECT camera maintains excellent prognostic value compared to conventional SPECT. However, information about the relationship between D-SPECT MPI and the prognosis in patients with ischemia and no obstructive coronary artery disease (INOCA) is limited. The objective of this study was to evaluate the prognostic value of MPI with D-SPECT in INOCA and obstructive coronary artery disease (CAD) patients. METHODS: All consecutive patients with suspected CAD and without prior CAD who underwent D-SPECT MPI and invasive coronary angiography within 3 months were considered. INOCA and obstructive CAD were defined as < 50% and ≥ 50% coronary stenosis, respectively. Patients were followed-up for the occurrence of major adverse cardiac events (MACE: cardiovascular death, nonfatal myocardial infarction, revascularization, stroke, heart failure and angina-related rehospitalization). RESULTS: Among 506 patients, 232 (45.8%) were INOCA patients. A total of 33.2% of the INOCA patients had abnormal D-SPECT MPI, whereas 77.7% of the obstructive CAD patients had abnormal D-SPECT MPI. In both groups, patients with abnormal D-SPECT MPI demonstrated higher MACE rates and lower survival free of MACE. In addition, patients with INOCA and abnormal D-SPECT MPI had a poor prognosis similar to that of the obstructive CAD patients. Cox regression analysis showed that the risk-adjusted hazard ratios for abnormal D-SPECT MPI were 2.55 [1.11-5.87] and 2.06 [1.03-4.10] in the INOCA and obstructive CAD patients, respectively. CONCLUSIONS: D-SPECT MPI provides excellent prognostic information, with a more severe prognosis in patients with abnormal D-SPECT MPI. INOCA patients with abnormal D-SPECT MPI experience a poor prognosis similar to that of patients with obstructive CAD.

Effect of Secondary Prevention Medication on the Prognosis in Patients With Myocardial Infarction With Nonobstructive Coronary Artery Disease.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) has been and remained a puzzling clinical entity. The role of secondary prevention therapy in patients with MINOCA remains unclear. This study aimed to evaluate the associations between secondary prevention medications and outcomes in patients with MINOCA. A total of 259 patients with MINOCA were consecutively enrolled. Basic information and medication of patients were assessed. We defined major adverse cardiovascular events as the primary end point and angina rehospitalization as the secondary end point. Logistic regression models were used to assess the correlation between treatment and outcomes. The proportion of statins, aspirin, clopidogrel, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEI/ARB), and ß-blocker used at admission was 88.8%, 86.9%, 84.6%, 51.7%, and 61.4%, respectively. At discharge, patients with MINOCA were less likely to be released on statins, aspirin, clopidogrel, ACEI/ARB, and ß-blocker. The use of secondary prevention medications was significantly lower at 2 years of follow-up with the most significant reductions being clopidogrel 29.4%, ACEI/ARB 39.0%, and aspirin 42.3%. About 19.1% of patients with MINOCA suffered adverse events during the follow-up period. Adverse events risk decreased when statins and ACEI/ARB were used, whereas the risk of adverse events was not lower in patients with aspirin, clopidogrel, and ß-blocker. In conclusion, patients with MINOCA were less likely to receive secondary prevention medications at the time of discharge and early discontinuation of medications at the time of follow-up. Statins and ACEI/ARB were the only medications substantially associated with lower adverse events; by comparison, aspirin, clopidogrel, and ß-blocker seem to have no impact on prognosis.

Myocardial Infarction with Nonobstructive Coronary Arteries (MINOCA): A Review of the Current Position.

Myocardial infarction with nonobstructive coronary arteries (MINOCA) remains a puzzling clinical entity that is characterized by clinical evidence of myocardial infarction (MI) with normal or near-normal coronary arteries on angiography (stenosis <50%). Major advances in understanding this condition have been made in recent years. The precise pathogenesis is poorly understood and is being studied and examined further. Guidelines indicate that MINOCA is a group of heterogeneous diseases with different mechanisms of pathology. Since there are multiple possible pathological mechanisms, it is not certain that the classical secondary prevention and treatment strategy for MI with obstructive coronary artery disease (MI-CAD) is optimal for MINOCA patients. The prognosis and predictors for MINOCA patients remain unclear. Although the prognosis is slightly better for MINOCA patients than for MI-CAD patients, MINOCA isn't always benign. The aim of this paper was to review the literature and evaluate MINOCA epidemiology, clinical features, etiology, diagnosis, treatment, and prognosis.

The MEDEA FAR-EAST Study: Conceptual framework, methods and first findings of a multicenter cross-sectional observational study.

BACKGROUND: The substantial increase in cardiovascular diseases (CVD) in China over the last three decades warrants comprehensive preventive primary and secondary strategies. Prolonged prehospital delay (PHD) has been identified as a substantial barrier to timely therapeutic interventions for acute myocardial infarction (AMI). Despite worldwide efforts to decrease the patient's decision-making time, minimal change has been achieved so far. Here, we aim to describe the conceptual framework and methods and outline key data of the MEDEA FAR-EAST Study, which aimed to elucidate in-depth barriers contributing to delay in Chinese AMI-patients. METHODS: Data sources of this multicenter cross-sectional observational study are a standardized bedside interview, a self-administered tailored questionnaire tool and the patient chart. PHD was defined as the main outcome and triangulated at bedside. Standard operation procedures ensured uniform data collection by trained study personnel. The study was ethically approved by Tongji-Hospital and applied to all participating hospitals. RESULTS: Among 379 consecutively screened patients, 296 (78.1%) fulfilled eligibility criteria. A total of 241 (81.4%) AMI-patients were male and 55 (18.6%) female. Mean age was 62.9 years. Prehospital delay time was assessed for 294 (99.3%) patients. Overall median PHD was 151 min with no significant sex difference. Symptom mismatch was present in 200 (69.7%) patients and 106 (39.0%) patients did not attribute their symptoms to cardiac origin. A total of 33 (12.4%) patients suffered from depression, 31 (11.7%) from anxiety and 141 (53.2%) patients employed denial as their major coping style. CONCLUSION: This is the first study on prehospital delay with emphasis on psychological variables in Chinese AMI-patients. A comprehensive assessment tool to measure clinical and psychological factors was successfully implemented. Socio-demographic key data proved a good fit into preexisting Chinese literature. Potential barriers including cardiac denial and symptom-mismatch were assessed for the first time in Chinese AMI-patients. The pretested selection of instruments allows future in depth investigations into barriers to delay of Chinese AMI-patients and enables inter-cultural comparisons.

Coronary Angiography-Derived Index of Microcirculatory Resistance Associated With New-Onset Atrial Fibrillation in Patients With STEMI.

BACKGROUND: Coronary angiography-derived index of microcirculatory resistance (caIMR) can effectively assess coronary microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). This study aimed to explore the role of caIMR in the occurrence of new-onset atrial fibrillation (NOAF) in patients with STEMI. METHODS: This was a single-centre retrospective clinical observational study. Patients diagnosed with STEMI from September 2019 to December 2022 were included. caIMR was calculated using computational flow and pressure simulations. During admission, suspicious heart rhythm was recorded by electrocardiographic (ECG) monitoring, and NOAF was confirmed by an immediate 12-lead ECG. RESULTS: A total of 739 patients were enrolled, including 57 (7.7) with NOAF. caIMR was significantly correlated with microvascular obstruction (R = 0.604; P < 0.001) and infarct size (R = 0.514; P < 0.001). After adjusting for potential confounding factors, the results showed that caIMR (odds ratio 1.058, 95% confidence interval 1.035-1.083; P < 0.001) was an independent risk factor for NOAF in patients with STEMI. Receiver operating characteristic analysis showed that the area under the curve of caIMR for predicting NOAF was 0.716. Compared with the caIMR < 27.35 U group, the caIMR ≥ 27.35 U group had higher high-sensitivity troponin T and N-terminal pro-B-type natriuretic peptide levels. When caIMR was added to the model, the reclassification and discriminant abilities improved significantly. CONCLUSIONS: Higher caIMR was an independent risk factor for NOAF in patients with STEMI. The caIMR had high specificity and sensitivity for predicting NOAF in patients with STEMI. The integration of caIMR into clinical risk factors showed significantly increased predictability for NOAF in patients with STEMI.