Independent Predictor Of Major Adverse Cardiovascular Events Research Articles

Prognostic value of cardiac magnetic resonance imaging parameters in left ventricular noncompaction with left ventricular dysfunction

BackgroundCardiac magnetic resonance (CMR) has been used to diagnose and risk-stratify patients with left ventricular noncompaction (LVNC). The prognostic value of CMR parameters for LVNC, especially feature tracking (CMR-FT), is not well known in LVNC patients with left ventricular dysfunction. The present study aimed to investigate whether the combination of CMR-FT with traditional CMR parameters can increase the prognostic value of CMR for LVNC patients with reduced left ventricular ejection fraction (LVEF).MethodsA total of 123 candidates were retrospectively included in this multicenter study and 55 LVNC patients (mean age, 45.7 ± 16.2 years; 61.8% men) remained after applying the exclusion criteria. Clinical features, left ventricular (LV) function parameters, global and segment myocardial strain, and late gadolinium enhancement (LGE) were evaluated. The outcomes include the composite events of cardiovascular death, heart transplantation, hospitalization for heart failure, thromboembolic events, and ventricular arrhythmias.ResultsAfter a median follow-up of 5.17 years (interquartile range: 0.17 to 10.58 years), 24 (36.8%) patients experienced at least one major adverse cardiovascular event (MACE). The myocardial strain parameters of patients with events were lower than those of patients without events. In the univariable Cox analysis, LVEF, the presence of LGE, global longitudinal strain (GLS) and segmental strains, including longitudinal strain at the apical level and radial and circumferential strain at the basal level, were significantly associated with MACEs. In the multivariate analysis, LGE (hazard ratio (HR) 3.452, 95% CI 1.133 to 10.518, p = 0.029) was a strong predictor of MACEs and significantly improved the predictive value (chi-square of the model after adding LGE: 7.51 vs. 13.47, p = 0.009). However, myocardial strain parameters were not statistically significant for the prediction of MACEs after adjusting for age, body mass index, LVEF and the presence of LGE and did not increase the prognostic value (chi-square of the model after adding GLS: 13.47 vs. 14.14, p = 0.411) in the multivariate model.ConclusionsThe combination of CMR-FT with traditional CMR parameters may not increase the prognostic value of CMR in LVNC patients with reduced LVEF, while the presence of LGE was a strong independent predictor of MACEs and significantly improved the predictive value.

Association of GNRI, NLR, and FT3 with the Clinical Prognosis of Older Patients with Heart Failure.

We investigated the relationship between heart failure and malnutrition, inflammation, and thyroid function and evaluated the predictive potential of these markers for major adverse cardiovascular events (MACEs).This study included 454 patients aged over 65 years with heart failure as the main diagnosis for 18 months follow-up. The nutritional and inflammatory status were assessed using the geriatric nutritional risk index (GNRI) and neutrophil-to-lymphocyte ratio (NLR), respectively. Free triiodothyronine (FT3) in thyroid hormone was divided into low, medium, and high FT3. Older patients were divided into two groups according to whether they had endpoint events. Differences in nutrition, inflammation, and thyroid hormone were compared between the two groups. The prognostic value of the combination of GNRI, NLR, and FT3 was analyzed.Older patients in the MACEs (+) group had lower levels of GNRI and FT3 and higher NLR than those in the MACEs (-) group. Low GNRI and FT3 and high NLR were associated with MACEs (P < 0.05). Multivariate Cox regression analysis revealed that low FT3 was an independent predictor of MACEs (P < 0.05). Regardless of how the LVEF changed, when patients had low GNRI and FT3 and high NLR risk factors, the risk of developing MACEs significantly increased. The addition of GNRI, NLR, and FT3 to the basic model significantly increased the predictability of MACEs in patients.Low GNRI and FT3 and high NLR were associated with MACEs. The combination of GNRI, NLR, and FT3 increased the predictive value of MACEs in older patients with heart failure.

Abstract 11766: Impact of Increasing Stent Length on Long-Term Clinical Outcomes Undergoing Intracoronary Imaging-Guided Percutaneous Coronary Intervention With New-Generation Drug-Eluting Stents

Background: While longer stent length of first-generation drug-eluting stents (DES) has been associated with stent-related adverse events, the association between stent length of new-generation DES and clinical outcomes remains controversial. Methods and Results: Consecutive 1403 patients including 2277 lesions who underwent intracoronary imaging-guided percutaneous coronary intervention with 2nd- and 3rd-generation DES were enrolled. Patients were divided into two groups according to total stent length (TSL), and followed up for major adverse cardiovascular events (MACE), defined as a composite of cardiac death, non-fatal myocardial infarction and target lesion revascularization (TLR) for patients. Lesions were divided into two groups according to TSL as well, and followed up for TLR and stent thrombosis. In the per patient analysis, long TSL group (TSL ≥ 32 mm, n = 703) had higher prevalence of diabetes (54.5% vs. 45.2%, P &amp;lt 0.001), anemia (48.4% vs. 43.0%, P = 0.042), peripheral artery disease (&amp;lt% vs. 10.6%, P = 0.003), multi-vessel disease (64.7% vs. 36.2%, P &amp;lt 0.001) and chronic total occlusion (9.5% vs 3.4%, P 0.001) than short TSL group (TSL &amp;lt 32 mm, n = 691). In the follow up period (mean of 1528 days), MACE and TLR were significantly higher in long TSL group than in short TSL group (P = 0.009 and P = 0.037, respectively). In the multivariate analysis after adjusting for confounding factors, the long TSL was an independent predictor of MACE and TLR (hazard ratio [HR] 1.59, P = 0.002 and HR 1.74, P = 0.047). In the per lesion analysis, Kaplan-Meier curve revealed that TLR was significantly higher in long TSL group (TSL ≥ 26 mm, n = 1160) than short TSL group (TSL &lt; 26mm, n = 1117) (P = 0.017), while stent thrombosis was comparable between the two groups. In the multivariate analysis, TLR was an independent predictor of TLR (HR 1.62, P = 0.029). Conclusion: Longer stent length of new-generation DES was associated with MACE and TLR, but not with stent thrombosis.

Abstract 13368: Effect of Peripheral Endothelial Function Assessment in Improving the Risk Stratification of Major Cardiovascular Events Beyond CHA2DS2-Vasc

Introduction: Peripheral microvascular endothelial dysfunction (PMED) is a marker and precursor of atherosclerosis and is associated with an increased risk of cardiovascular events. The present study aims to identify the best cut-off value of PMED, assessed by the reactive hyperemia index, in predicting major adverse cardiovascular events (MACE). Additionally, we investigate whether integrating PMED to CHA2DS2-Vasc score improves the predicting accuracy of cardiovascular disease. Methods: this is a retrospective study of patients who underwent reactive hyperemia peripheral arterial tonometry (PAT). The optimal cut-off value of reactive hyperemia index associated with MACE was calculated using the area under the receiver-operating curve and the maximum Youden index. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, vascular disease were determined to calculate the CHA2DS2-VASc score. MACE was defined as myocardial infarction, heart failure hospitalization, and cerebrovascular events. Results: 1,690 patients were enrolled (average age 51.1±13.9, 64.1% female). The optimal cut-off value of the reactive hyperemia index was 2.0 in the overall population and females and 2.17 in males. The risk of MACE during 10 (Interquartile range: 4,16) years of follow-up was 15.3%. Multivariable logistic regression revealed that PMED as an independent predictor of MACE (PMED: OR, 3.6, 95% CI, 2.6-4.9, p&lt;0.001) (Table1). Furthermore, integrating PMED to CHA2DS2-VASc significantly improved the predictive accuracy (area under the curve, 0.747 vs. 0.708, p&lt;0.001). Conclusion: PMED is a strong predictor of cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Abstract 14424: Comparative Evaluation of Various Risk Scores in Non-ST-Segment Elevation Myocardial Infarction

Introduction: Risk stratification is an integral component of the management strategy in patients with non-ST-elevation myocardial infarction (NSTEMI). Multiple risk scores have been proposed however, these have not been validated in developing countries such as India. Hypothesis: This study aims to determine the various prognostic factors in patients with NSTEMI as well as to compare and validate the performance of different risk stratification scores in these subjects. Methods: This was a single center prospective observational study wherein diagnosed with NSTEMI were enrolled. A detailed clinical history including symptomatology, presence of risk factors and family history were recorded. In all enrolled patients based on the prospectively collected data, five risk scores i.e. TIMI, GRACE version 2.0, PURSUIT, HEART and CAMI-NSTEMI were computed. Outcome data in terms of both in-patient as well as at 14 days, six months and one year major adverse cardiovascular events (MACE) were obtained. Results: A total of 1102 patients were enrolled with a mean age of 59.6 ± 11.2 years. MACE occurred in 140/1102 subjects (12.7%) with mortality in 89 (8.1%) patients. Patients with MACE were elderly, had higher frequency of smoking, hypertension, diabetes and stroke. Multivariate logistic regression analysis revealed that angina in last 48 hours, diabetes, smoking, cardiac arrest on presentation and fragmented QRS on ECG were independent predictors of MACE. All risk scores were able to predict MACE events equally well however, for in-hospital MACE, TIMI risk score had the highest predictive ability. However, for 14-day, 6 month and one year MACE, GRACE scores had highest predictive ability. Conclusions: Our study showed that all risk scores had a good predictive ability for both short term as well as intermediate-term MACE events.

Abstract 10038: Combined Low Endothelial Shear Stress and High Plaque Structural Stress Heterogeneity Predicts Non-Culprit Major Adverse Cardiovascular Events; Insights From the PROSPECT Study

Introduction: Low endothelial shear stress (ESS) is a pro-atherogenic stimulus associated with coronary plaque development, while high plaque structural stress (PSS) and its heterogeneity is associated with plaque destabilization. Previous studies showed that combining ESS and PSS additively predicts plaque progression, but no studies have determined their ability to predict major adverse cardiovascular events (MACE). We examined whether combining ESS and PSS improves MACE prediction in patients with acute coronary syndrome. Methods: We examined baseline ESS, ESS gradient, PSS, and PSS heterogeneity index (HI) in 22 non-culprit lesions (NCL) leading to future MACE, and 64 randomly selected control NCLs without MACE from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. ESS was calculated by computational fluid dynamics and PSS by finite element analysis on co-registered lesions. Results: 86 lesions (55 thin-cap and 31 thick-cap fibroatheromas) were analyzed from 67 patients. Lesions that caused future MACE showed baseline higher PSS HI (0.32 vs. 0.24, p&lt;0.001), lower ESS (0.56 vs. 0.91 Pa, p=0.007), higher ESS gradient (3.82 vs. 1.96 Pa/mm, p=0.007), smaller minimum lumen area (MLA, 3.83 vs. 5.05 mm 2 , p=0.002), and larger plaque burden (PB, 70% vs. 59.4%, p&lt;0.001). Independent predictors of MACE in multivariate analysis included high PSS HI (hazard ratio [HR] 3.9, 95% confidence interval [CI] 1.5-10.4, p=0.006), high ESS gradient (HR 3.4, 95% CI 1.4-8.1, p=0.007), and high PB at the MLA (HR 2.6, 95% CI 1.1-6.3, p=0.035). Combining low ESS and high PSS HI improved test specificity to 0.83 and positive predictive value (PPV) to 59.3%, while maintaining high sensitivity at 0.73 and high negative predictive value (NPV) at 89.8%. Combining low ESS, high ESS gradient, and high PSS HI further improved prognostication, predicting 80% of MACE over 3-year follow-up (p&lt;0.001). Conclusions: Combining baseline low ESS, high ESS gradient and high PSS heterogeneity significantly improves risk stratification of NCLs over each parameter alone. Combining parameters exceeds PPV and NPV achieved by imaging alone, and may identify lesions suitable for preemptive intervention strategies to avert future MACE.

Abstract 10946: Myocardial Inflammatory Activity and Oxidative Stress Immunosuppressive Therapy Are Associated With Prognosis in Patients With Cardiac Sarcoidosis

Background: P atients with cardiac sarcoidosis (CS) have been shown to be at an increased risk of major adverse cardiovascular events (MACE). Enhancement in myocardial inflammatory activity and oxidative stress is a crucial cause of MACE. Immunosuppressive therapy is recommended for the treatment of active CS. After immunosuppressive therapy, however, there is no predictable markers for prognosis. We hypothesized that the inflammation and oxidative stress in heart were associated with MACE. Aim: We identified prognostic markers for MACE in patients with CS after steroid therapy. Methods: This prospective cohort study enrolled 103 consecutive patients with CS diagnosed according to the Japanese guideline; Of 103 CS patients, 39 patients underwent 18F-FDG PET/CT 6 months after steroid therapy, and levels of urinary 8-hydroxy-2′-deoxyguanosine (U-8-OHdG) as a marker of oxidative DNA damage, other biomarkers, indices of cardiac function, and renal function were measured. Then they were followed up for a median of 42 months. The primary endpoint was a composite of the first sustained ventricular tachycardia (sVT) /sudden cardiac death (SCD), hospitalization for heart failure, and worsening CS with increased accumulation of FDG in heart and exacerbation of clinical manifestation. Results: During the follow-up period, 7 of 30 patients showed sVT/SCD (N= 9), hospitalization (N= 2) and worsening CS (N= 4). A Cox proportional-hazard model showed that U-8-OHdG concentration and SUV max value of FDG-PET were independent predictors of MACE. ROC analysis showed that the cut-off values of U-8-OHdG and SUV max for predicting the MACE were 14.2 ng/mg·Cr and 4.6 respectively. Patients with a U-8-OHdG ≥ 14.2 ng/mg·Cr or SUV max ≥4.6 had a significantly higher MACE risk (Figure A and B). Conclusions: U-8-OHdG and SUV max after steroid therapy were powerful predictors of MACE in CS, suggesting that CS patients with high U-8OHdG and/or high SUV max might be resistant to steroid therapy.

Acute kidney injury as the most important predictor of poor prognosis after interventional treatment for aortic stenosis.

Aortic stenosis (AS) is the most common acquired valvular disease. There are two methods of interventional treatment: surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI). The choice between SAVR and TAVI depends on the assessment of individual perioperative risk and long-term treatment outcomes. It is essential to identify factors that may influence the outcomes of the treatment to minimize their negative effects. The study aimed to identify the most important risk factor which affects treatment outcomes in patients with AS undergoing SAVR/TAVI. This study reviewed retrospectively patients with AS who underwent SAVR or TAVI. The primary outcomes included incidences of major adverse cardiovascular events (MACE) defined as cardiovascular death, stroke, and hospitalization for cardiovascular issues assessed over a one-year follow-up period. An occurrence of postprocedural AKI (acute kidney injury) was identified as an independent predictor of MACE. The study included 78 patients, with the same number of subjects in each group (SAVR/TAVI [n = 39]). Twenty-nine patients developed AKI. It was similar in both groups (SAVR [n = 15]; TAVR [n = 14]). In the SAVR group, 13 (33%) patients developed at least one MACE compared to 5 (13%) patients in the TAVI group. AKI and the type of procedure (SAVR) were shown to be significantly and independently associated with the development of MACE (P = 0.01 and P = 0.03, respectively) as shown in the Cox multivariable regression model. Our study demonstrated that AKI is the strongest predictor of major adverse cardiovascular events after using both methods of aortic valve replacement (SAVR/TAVI).

High-Sensitivity C-Reactive Protein-to-Albumin Ratio in Predicting the Major Adverse Cardiovascular Event in Acute Coronary Syndrome at Presentation

Objective: Our study aimed to determine the association between high sensitivity-c reactive protein to albumin ratio (CAR) and in-hospital major adverse cardiovascular event (MACE) in patients with acute coronary syndrome and also to assess whether hs-CAR is a better marker than hsCRP or albumin alone in predicting MACE. Materials and Methods: We enrolled 110 cases who were hospitalized and major adverse cardiovascular event was defined as cardiogenic shock, acute heart failure, reinfarction and death. Blood sample for Serum albumin and hs-crp was taken at the time when patients were admitted. Results: The incidence of MACE was more in patients with high CAR (≥1.8 group) as compared to those with low CAR (&lt;1.8 group). Conclusion: The CAR is an independent predictor of MACE in patients who present with ACS.

New R2-CHA2DS2-VASc score predicts no-reflow phenomenon and long-term prognosis in patients with ST-segment elevation myocardial infarction after primary percutaneous coronary intervention.

AimsEvaluating the prognostic validity of new R2-CHA2DS2-VASc score for no-reflow phenomena and long-term prognosis in patients following primary percutaneous coronary intervention (PCI) with ST-elevation myocardial infarction (STEMI).Materials and methodsFrom January 2017 to December 2018, a total of 401 patients with STEMI were continuously enrolled. According to the cut-off value, the patients were separated into two groups: R2-CHA2DS2-VASc < 3 group (n = 275) and R2-CHA2DS2-VASc ≥ 3 group (n = 126).ResultsWith a sensitivity of 52.6% and a specificity of 73.1%, the optimal cut-off value for predicting no-reflow is R2-CHA2DS2-VASc ≥ 3. R2-CHA2DS2-VASc ≥ 3 as the ideal cut-off value for predicting major adverse cardiovascular events (MACE) with an area under the curve (AUC) of 0.781 [95% Confidence interval (CI): 0.738–0.801, P 0.001], a sensitivity of 50%, and a specificity of 91.1%. The incidence of MACE, death from all causes, and worsening heart failure was greater in the R2-CHA2DS2-VASc ≥ 3 group, although there was no significant difference in the incidence of repeated revascularisation procedures following PCI between the two groups. R2-CHA2DS2-VASc ≥ 3 was also an independent predictor of MACE (hazard ratio = 2.48, 95% confidence interval CI: 1.33–4.62, P = 0.04). Moreover, this score has a greater sensitivity (66.7%) and specificity (88.7%) for predicting the progression of heart failure.ConclusionR2-CHA2DS2-VASc ≥ 3 was independently associated with no-reflow phenomenon and poor clinical outcomes for patients in STEMI after primary PCI.

Safety, feasibility, and prognostic value of stress perfusion CMR in patients with MR-conditional pacemaker.

To assess the safety, feasibility, and prognostic value of stress cardiovascular magnetic resonance (CMR) in patients with pacemaker (PM). Between 2008 and 2021, we conducted a bi-centre longitudinal study with all consecutive patients with MR-conditional PM referred for vasodilator stress CMR at 1.5 T in the Institut Cardiovasculaire Paris Sud and Lariboisiere University Hospital. They were followed for the occurrence of major adverse cardiovascular events (MACE) defined as cardiac death or non-fatal myocardial infarction. Cox regression analyses were performed to determine the prognostic value of CMR parameters. The quality of CMR was rated by two observers blinded to clinical details. Of 304 patients who completed the CMR protocol, 273 patients (70% male, mean age 71 ± 9 years) completed the follow-up (median [interquartile range], 7.1 [5.4-7.5] years). Among those, 32 experienced a MACE (11.7%). Stress CMR was well tolerated with no significant change in lead thresholds or pacing parameters. Overall, the image quality was rated good or excellent in 84.9% of segments. Ischaemia and late gadolinium enhancement (LGE) were significantly associated with the occurrence of MACE (hazard ratio, HR: 11.71 [95% CI: 4.60-28.2]; and HR: 5.62 [95% CI: 2.02-16.21], both P < 0.001). After adjustment for traditional risk factors, ischaemia and LGE were independent predictors of MACE (HR: 5.08 [95% CI: 2.58-14.0]; and HR: 2.28 [95% CI: 2.05-3.76]; both P < 0.001). Stress CMR is safe, feasible and has a good discriminative prognostic value in consecutive patients with PM.

Treatment and prognosis of elderly patients with non-ST-elevation myocardial infarction

Abstract Background/Introduction Elderly constitute a large though specific group of patients presenting with non-ST elevation myocardial infarction (NSTEMI), as they are at higher risk of adverse cardiovascular events, as well as treatment-related complications. However as they underrepresented in clinical trials, the optimal management strategy for older patients with NSTEMI remains unclear. Purpose The aim of this registry was to capture the medical and invasive treatment of elderly NSTEMI patients, find predictors for major adverse cardiovascular events (MACE) and estimate the impact of invasive management and revascularisation. Methods The POPular AGE registry is a prospective, observational multicentre study of patients ≥75 years of age presenting with NSTEMI at multiple sites in the Netherlands, United Kingdom and Austria. Management was at the discretion of the treating physician. MACE consisted of cardiovascular death, acute coronary syndrome (ACS) and stroke. Net adverse clinical events (NACE) was defined as composite of all-cause death, ACS, definite stent thrombosis, stroke, or major bleeding (Bleeding Academic Research Consortium [BARC] bleeding 3 or 5). The population was stratified into an invasively treated group defined as patients who underwent coronary angiography (CAG); and a conservatively-treated group with patients who received medical treatment only. The duration of follow-up was one year. Clinical variables were assessed for their predictive value for MACE and bleeding by means of a Cox proportional hazard regression. Results The total study population consisted of 1190 elderly patients with NSTEMI (median age 80 years [IQR 77–84], 43% female). Invasive treatment with CAG was performed in 67% of the population, of which 49% underwent PCI and 14% coronary artery bypass grafting (CABG). At discharge, the majority of patients (55%) were treated with dual antiplatelet therapy (DAPT). MACE occurred in 15% and major bleeding occurred in 5% of the total population. Age (HR 1.06, 95% CI 1.03–1.09), diabetes mellitus (HR 1.62, 95% CI 1.16–2.24), reduced LVEF (&amp;lt;50%) (HR 1.51, 95% CI 1.03–2.20), Killip class (HR 1.58, 95% CI 1.07–2.33) and electrocardiogram (ECG) changes at admission (HR 1.67, 95% CI 1.20–2.31) were predictors for MACE. MACE occurred more frequently in conservatively-treated than invasively-treated patients (20% vs. 12%, HR 0.52, 95% CI 0.38–0.70, p&amp;lt;0.001). Revascularization with PCI or CABG was associated with lower risk of MACE (PCI; HR 0.47, 95% CI 0.30–0.75, p=0.001 and CABG; HR 0.31, 95% CI 0.13– 0.73, p=0.008). Conclusions In this prospective registry of NSTEMI patients of ≥75 years, MACE and major bleeding were frequent. Age, diabetes mellitus, reduced LVEF, Killip class and ECG changes at admission were independent predictors for MACE. Although subject to selection bias, undergoing CAG and revascularisation, when indicated, were associated with better outcomes. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): AstraZeneca

Non-dipping heart rate &amp; major adverse cardiovascular events in type 2 diabetes mellitus

Abstract Background Type 2 diabetes mellitus (T2DM) is a known major risk factor for cardiovascular disease. Whilst the influence of traditional risk factors such as hypertension, hyperlipidaemia and smoking are well-established determinants of major adverse cardiovascular events (MACE) in subjects with T2DM, the impact of insulin resistance, non-dipping blood pressure and heart rate status have not been adequately investigated. Purpose To determine predictors of MACE in a population of T2DM with underlying target-organ damage at baseline. Methods This study included 196 subjects with T2DM with advanced proliferative diabetic retinopathy. These subjects were recruited in 2008–2009 and were consequently followed up till February 2022 to determine independent predictors of MACE. At baseline, the median age of the participants was 64 years (IQR: 59–71 years) and the median diabetes duration was 18 years (IQR: 10–25 years). At baseline, all underwent 24-hour blood pressure and heart rate (HR) monitoring, and were assessed for markers of inflammation, insulin resistance, albuminuria, presence of peripheral neuropathy and peripheral vascular disease. Subjects whose night-time HR did not decrease by more than 10% as compared to daytime readings were classified as non-dippers. Similarly, a non-dipping BP profile was defined as a nocturnal decline of mean arterial pressure of less than 10%. At follow-up, the all-cause death rate was noted as well as MACE. The latter was defined as all-cause death, non-fatal MI, non-fatal stroke, coronary revascularisation or hospitalisation for unstable angina pectoris or heart failure. Univariate followed by multivariate Cox-regression analysis was performed to determine independent predictors of both all-cause mortality and MACE. Results At follow-up, 46% of the study participants had died whilst 63.1% had exhibited MACE. Multivariate analysis revealed age (OR: 1.05, 95% CI 1.02–1.07, p&amp;lt;0.001), ESR (OR: 1.012, 95% CI: 1.001–1.02, p=0.035), GGT (OR: 1.005, 95% CI 1.001–1.009, p=0.025) and eGFR (OR: 0.99, 95% CI 0.98–0.99, p=0.016) at baseline to be independent determinants of all-cause death. With regards MACE, likewise, age (OR: 1.028, 95% CI 1.007–1.05, p=0.009), GGT (OR: 1.004, 95% CI 1.001–1.008, p=0.017) and eGFR (OR: 0.99, 95% CI 0.98–0.99, p=0.022) were shown to be independent determinants together with diabetes duration (OR: 1.034, 95% CI 1.014–1.055, p=0.001) and presence of non-dipping heart rate at baseline. The latter was shown to be the strongest predictor of MACE (OR: 1.55, 95% CI 1.06–2.26, p=0.024). Conclusion Whereas increasing age and impaired renal function are known risk factors for cardiovascular disease, this long-term follow-up study has highlighted the relevance of non-dipping heart rate in type 2 diabetes mellitus. Previous studies had shown an association between non-dipping heart rate and target-organ damage in diabetic subjects. The impact on MACE merits further investigation. Funding Acknowledgement Type of funding sources: None.

Incremental prognostic value of stress CMR for cardiovascular risk stratification after a cryptogenic ischemic stroke

Abstract Background One-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest of CAD screening in patients with cryptogenic stroke is still debated. Purpose The aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke. Methods Between 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia. Results Of 542 patients (55.2% male, mean age 71.4±8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18% and 17% of patients, respectively. Using Kaplan-Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE (hazard ratio, HR: 8.43 [95% CI: 5.11–13.9]; HR: 7.87 [95% CI: 4.80–12.9]; respectively, p&amp;lt;0.001). In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE (HR: 8.08 [95% CI: 4.21–15.5]; HR: 6.65 [95% CI: 3.49–12.7]; respectively, p&amp;lt;0.001). After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI=0.428; IDI=0.048). Conclusions In patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors. Funding Acknowledgement Type of funding sources: None.

Incremental prognostic value of stress CMR in symptomatic patients with coronary stenosis on CCTA

Abstract Background Noninvasive functional imaging is often performed in patients with obstructive coronary artery disease (CAD) on coronary computed tomography angiography (CCTA). However, the prognostic value of stress cardiovascular magnetic resonance (CMR) is unknown in patients with coronary stenosis of unknown significance on CCTA. Purpose To assess the prognostic value of stress CMR in symptomatic patients with obstructive CAD of unknown significance on CCTA. Methods Between 2008–2020, consecutive symptomatic patients without known CAD referred for CCTA were screened. Patients with obstructive CAD (at least 1 ≥50% stenosis on CCTA) were further referred for stress CMR and followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or nonfatal myocardial infarction. Results Of 2,210 patients who completed CMR, 2,038 (46.5% male, mean age 69.8±12.2 years) completed follow-up (median 6.8 [IQR 5.9–9.2] years); 281 experienced a MACE (13.8%). Inducible ischemia and late gadolinium enhancement (LGE) were significantly associated with MACE (HR: 4.51, [95% CI: 3.55–5.74]; and HR: 3.32, [95% CI: 2.55–4.32], respectively; p&amp;lt;0.001). In multivariable Cox regression, number of segments with &amp;gt;70% stenosis, with noncalcified plaques and number of vessels with obstructive CAD were prognosticators (p&amp;lt;0.001). The presence of inducible ischemia and LGE were independent predictors of MACE (HR: 3.97, [95% CI: 3.43–5.13]; HR: 2.30, [95% CI: 1.52–3.33]; p&amp;lt;0.001). After adjustment, stress CMR showed the best improvement in model discrimination and reclassification above traditional risk factors and CCTA (C-statistic improvement: 0.04; NRI=0.421; IDI=0.047). Conclusions In symptomatic patients with obstructive CAD of unknown significance on CCTA, stress CMR had incremental prognostic value to predict MACE. Funding Acknowledgement Type of funding sources: None.

Beta-Secretase-1 Antisense RNA Is Associated with Vascular Ageing and Atherosclerotic Cardiovascular Disease.

The noncoding antisense transcript for β-secretase-1 (BACE1-AS) is a long noncoding RNA with a pivotal role in the regulation of amyloid-β (Aβ). We aimed to explore the clinical value of BACE1-AS expression in atherosclerotic cardiovascular disease (ASCVD). Expression of BACE1-AS and its target, β-secretase 1 (BACE1) mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome). Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity, were measured as markers of subclinical ASCVD. Patients were followed for a median of 52 months for major adverse cardiovascular events (MACE). In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r = 0.396, p < 0.001) and marginally with Aβ1-40 levels in plasma (r = 0.141, p = 0.008). Higher BACE1-AS was associated with higher estimated CVD risk assessed by HeartScore for non-CVD subjects and by European Society of Cardiology clinical criteria for the total population (p < 0.05 for both). BACE1-AS was associated with higher prevalence of CAD (odds ratio [OR] = 1.85, 95% confidence interval [CI]: 1.37-2.5), multivessel CAD (OR = 1.36, 95% CI: 1.06-1.75), and with higher number of diseased vascular beds (OR = 1.31, 95% CI: 1.07-1.61, for multiple diseased vascular beds) after multivariable adjustment for traditional cardiovascular risk factors. In the prospective arm, BACE1-AS was an independent predictor of MACE in high cardiovascular risk patients (adjusted hazard ratio = 1.86 per ascending tertile, 95% CI: 1.011-3.43, p = 0.046). BACE1-AS is associated with the incidence and severity of ASCVD.

Additional prognostic value of stress cardiovascular magnetic resonance for cardiovascular risk stratification after a cryptogenic ischemic stroke.

BackgroundOne-third of ischemic strokes are “cryptogenic” without clearly identified etiology. Although coronary artery disease (CAD) is the main cause of death after stroke, the interest in CAD screening in patients with cryptogenic stroke is still debated.AimThe aim of the study was to assess the incremental prognostic value of stress cardiovascular magnetic resonance (CMR) beyond traditional risk factors for predicting cardiovascular events in patients with a prior cryptogenic ischemic stroke.Materials and methodsBetween 2008 and 2021, consecutive patients with prior cryptogenic strokes referred for stress CMR were included and followed for the occurrence of major adverse cardiovascular events (MACEs), defined by cardiovascular death or non-fatal myocardial infarction (MI). Univariable and multivariable Cox regressions were performed to determine the prognostic value of unrecognized MI and silent ischemia.ResultsOf 542 patients (55.2% male, mean age 71.4 ± 8.8 years) who completed the follow-up (median 5.9 years), 66 (12.2%) experienced MACE. Silent ischemia and unrecognized MI were detected in 18 and 17% of patients, respectively. Using Kaplan–Meier analysis, silent ischemia and unrecognized MI were associated with the occurrence of MACE [hazard ratio, HR: 8.43 (95% CI: 5.11–13.9); HR: 7.87 (95% CI: 4.80–12.9), respectively, p < 0.001]. In multivariable analysis, silent ischemia and unrecognized MI were independent predictors of MACE [HR: 8.08 (95% CI: 4.21–15.5); HR: 6.65 (95% CI: 3.49–12.7), respectively, p < 0.001]. After adjustment, stress CMR findings showed the best improvement in model discrimination and reclassification above traditional risk factors (C-statistic improvement: 0.13; NRI = 0.428; IDI = 0.048).ConclusionIn patients with prior cryptogenic stroke, stress CMR findings have an incremental prognostic value to predict MACE over traditional risk factors.

Prognostic value of plasma adipokine chemerin in patients with coronary artery disease

BackgroundAdipokine chemerin was proven to be associated with coronary artery disease (CAD), but its prognostic implications in CAD remain unclear.MethodsThis study consists of two parts, one is a basic study and the other is a clinical cohort study. First, we investigated the differential expression of six adipokines in the atherosclerotic mice model compared to mice with milder degrees of atherosclerosis and mice without atherosclerosis using microarray data. We then examined the potential of chemerin as a diagnostic and prognostic indicator in a CAD cohort. A total of 152 patients were enrolled in our study, including 77 patients with angiographically proven CAD and 75 control subjects without cardiovascular disease. Plasma adipokine chemerin levels were measured in all patients, and major adverse cardiovascular events (MACEs) were followed up, including ischemic stroke, non-fatal myocardial infarction, revascularization, and cardiovascular death.ResultsIn the aortas of atherosclerotic mice, chemerin expression was up-regulated compared to control mice. The plasma chemerin levels of CAD patients were higher than those of non-CAD patients (128.93 ± 37.06 vs. 109.85 ± 27.47 mmol/L, respectively, P < 0.001). High chemerin levels were an independent predictor of CAD (β = 2.702, 95% CI, 1.344–5.431, P = 0.001). We followed up with patients for a median duration of 5.5 years (3.9–5.6). The Kaplan–Meier curves showed that patients in the high chemerin group had a significantly higher risk of MACEs than the low chemerin group in patients with CAD (log-rank P = 0.003), not with non-CAD (Log-rank P = 0.120). Furthermore, Cox multivariate analysis revealed that high chemerin levels were an independent predictor of MACEs (HR 2.267; 95% CI, 1.139–4.515; P = 0.020). Finally, the cellular study showed that chemerin is predominantly expressed in PBMC-derived macrophages.ConclusionPlasma chemerin levels were increased in the CAD patients, and a high chemerin level increased the risk of MACEs in CAD patients.

Predictive value of baseline C-reactive protein level in patients with stable coronary artery disease: A meta-analysis.

Background:Conflicting results have been reported on the association of C-reactive protein (CRP) level with adverse outcomes in patients with stable coronary artery disease (CAD). The objective of this meta-analysis was to evaluate the predictive value of baseline CRP level in stable CAD patients.Methods:Two reviewers independently searched PubMed and Embase databases from their inception to November 28, 2021 to identify studies assessing the value of baseline CRP level in predicting adverse outcomes in stable CAD patients. The endpoints of interest included cardiovascular mortality, all-cause mortality, or major adverse cardiovascular events (MACEs). The predictive value of CRP level was estimated by pooling the multivariable adjusted risk ratio with 95% confidence intervals (CI) compared the highest to the lowest CRP level.Results:Twenty-six studies involving of 22,602 patients with stable CAD satisfied the inclusion criteria. In a comparison of the highest with the lowest CRP level, the pooled multivariable adjusted risk ratio was 1.77 (95% CI 1.60–1.96) for MACEs, 1.64 (95% CI 1.13–2.33) for cardiovascular mortality, and 1.62 (95% CI 2.62–5.12) for all-cause mortality, respectively. Subgroup analyses indicated that the values of elevated CRP level in predicting MACEs were consistently observed in each subgroup.Conclusion:Elevated baseline CRP level was an independent predictor of MACEs, cardiovascular mortality, and all-cause mortality in patients with stable CAD. Baseline CRP level can provide important predictive information in stable CAD patients.

Association of serum levels of osteopontin and osteoprotegerin with adverse outcomes after endovascular revascularisation in peripheral artery disease

BackgroundOsteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD).Methods203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups.ResultsDuring 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p < 0.001) and OPN (79.99 ± 38.29 ng/ml vs 35.21 ± 14.84 ng/ml, p < 0.001) levels were significantly higher in PADG compared to COG, as well as in MACE subgroup compared to non-MACE subgroup (13.29 ± 3.23 ng/ml vs 10.86 ± 3 ng/ml and 96.45 ± 40.12 ng/ml vs 78.1 ± 38.29 ng/ml, respectively). An independent association of PAD with OPG and OPN was found in the whole patient cohort. Although OPG and OPN were significantly related to MACE incidence in the univariate analysis, multiple logistic regression analysis failed to detect any independent predictor of MACE within the PADG.ConclusionBaseline high OPG and OPN levels were independently associated with PAD presence. Even higher levels of those biomarkers were detected among PAD patients with MACE, however, their prognostic role should be further clarified.