Search Results (125)

Background and Objectives: Cardiovascular (CV) diseases account for about 32% of deaths in women, with differing risk factors between women and men. Our study aimed to compare sex-related risk factors and comorbidities in patients at very high CV risk. Materials and Methods: We consecutively enrolled adult patients hospitalized for myocardial infarction or unstable angina at a tertiary referral center in western Romania between October 2016 and June 2017. A total of 299 adults underwent clinical and biochemical evaluations between 6 months and 2 years after their coronary event. We assessed patients’ specific characteristics, comorbidities, and risk factors. Results: Women made up only a quarter of the survey participants (74 women, 24.7%) and were generally older (63.32 ± 9.3 vs. 60.51 ± 9.3, p = 0.02) and more obese (31.20 ± 6.0 vs. 29.48 ± 4.9, p = 0.02). There were no significant differences in the prevalence of hypertension, diabetes, dyslipidemia, chronic kidney disease, or peripheral artery disease, though women had slightly higher rates for most comorbidities. Regarding smoking habits, both groups had high percentages of current and former smokers, with women being significantly less likely to smoke (20.9% vs. 44.6%, p = 0.003). Multivariable logistic regression adjusting for age, BMI, smoking status, diabetes, and eGFR revealed that sex was not a statistically significant independent predictor for myocardial infarction, PCI, or CABG. Conclusions: We observed that women with previous coronary events had a worse risk factor profile, while there were no significant sex differences in overall comorbidities. Risk factor control should be based on sex-specific prediction models. Full article

Background: Although contemporary stent technology has significantly evolved, a substantial number of patients present with stent failure (SF), the clinical expression of which is either in-stent restenosis (ISR) or stent thrombosis (ST). Methods: In this observational, single-center study, we aimed to compare the clinical characteristics, clinical presentation, angiographic findings and subsequent management of patients who underwent percutaneous coronary intervention (PCI) for SF, either ISR or ST, with patients who had PCI for de novo lesions. Results: Over a period of two years (September 2022–October 2024), 1120 patients underwent PCI, of whom 9% had SF. Of the 101 SF cases, the majority (76 cases, 75%) had ISR, while the rest (25 cases, 25%) had ST. Regarding baseline characteristics, patients who underwent PCI for SF had a higher incidence of diabetes mellitus (53% vs. 29%; p < 0.001), dyslipidemia (88% vs. 50%; p < 0.001) as well as prior coronary artery bypass grafting surgery (7.9% vs. 3.7%; p = 0.043), while they were less likely to be current smokers (33% vs. 52%; p < 0.001). SF PCI patients presented more frequently with unstable angina (17% vs. 8.9%; p = 0.010). A new stent was implanted in less than half of SF cases (i.e., stent implantation, 44% vs. 91%; p < 0.001). On the other hand, in the clinical setting of SF, drug-coated balloons (44% vs. 5.3%; p < 0.001) and plain balloon angioplasty (8.9% vs. 0.7%; p < 0.001) was applied more frequently compared with de novo lesions. Furthermore, the usage of cutting/scoring balloons and lithotripsy was significantly higher in the SF group (8.9% vs. 0.4% and 12% vs. 3%, respectively; p < 0.001 for both). Intracoronary imaging guidance was more commonly used in the SF group (33% vs. 13%; p < 0.001). Stent malapposition (44%) and neoatherosclerosis (67%) were the most common mechanisms of ST and ISR, respectively, as identified by intravascular imaging modalities. Finally, the success rates were comparable (96% vs. 98%; p = 0.150) between the two groups. Conclusions: Approximately one of ten patients underwent PCI because of the failure of a previously implanted stent. Use of intracoronary imaging is significantly higher in the clinical context of SF. While DES implantation remains the standard of practice for de novo lesions, DCBs are a popular alternative, especially for ISR cases. Interventional cardiologists who are involved in the treatment of SF cases should be familiar with interpreting intravascular imaging to guide the use of the adjunctive device required to ensure that optimal procedural results in SF cases are obtained. Full article

Background: Coronary artery disease (CAD) is a leading global cause of mortality. The role of calcium (Ca), a key metabolic and structural element, in atherosclerosis and inflammation remains unclear. Ca influences immune cell function and is a component of atherosclerotic plaques. Hair analysis reflects long-term mineral exposure and may serve as a non-invasive biomarker. Objectives: This pilot study aimed to investigate the association between hair Ca levels and acute coronary syndrome (ACS), and to evaluate correlations with the Systemic Inflammatory Index (SII), Systemic Inflammatory Response Index (SIRI), and selected CAD risk factors. Methods: Ca levels were measured in hair samples from patients undergoing coronary angiography for suspected myocardial infarction. Associations with ACS diagnosis, Syntax score, SII, SIRI, and CVD risk factors were analyzed. Results: Serum calcium levels were not significantly associated with the presence of acute coronary syndrome (ACS) (p = 0.392) or with its clinical subtypes, including ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), and unstable angina (UA) (p = 0.225). Diagnosis of ACS was linked to higher SII (p = 0.028) but not SIRI (p = 0.779). Ca levels correlated negatively with Syntax score (R = −0.19, p = 0.035) and SII (R = −0.22, p = 0.021) and positively with HDL-C (R = 0.18, p = 0.046). Conclusions: Hair calcium content may reflect subclinical inflammation and CAD severity. Although no direct link to ACS was observed, the associations with SII, HDL-C, and Syntax score suggest a potential diagnostic role which should be further explored in larger, well-controlled studies. Full article

Acute coronary syndrome (ACS) refers to a spectrum of conditions characterized by a sudden decrease in blood flow to the heart. This includes unstable angina, the mildest form, as well as non-ST- and ST-segment elevation myocardial infarction. The primary cause of ACS is typically the rupture or erosion of an atherosclerotic plaque in a coronary artery, resulting in the formation of a blood clot that can, partially or completely, block the blood flow to the heart muscle. The ongoing discovery and comprehension of emerging biomarkers for atherosclerosis could enhance our capacity to predict future events, particularly when integrated alongside traditional risk factors in assessing overall risk profiles. With advancements in proteomic technologies, large-scale approaches have been increasingly instrumental in unraveling pathways implicated in atherosclerotic degeneration and identifying novel circulating markers, which may serve as early diagnostic indicators or targets for innovative therapies. Over recent decades, numerous matrices including plasma, urine, microparticles, lipoproteins, atherosclerotic plaque extracts and secretomes, as well as thrombi, have been examined to address these questions. Furthermore, proteomics has been applied to various experimental models of atherosclerosis to deepen our understanding of the mechanisms underlying atherogenesis. This review offers a critical overview of the past two decades of untargeted omics research focused on identifying circulating and tissue biomarkers relevant to ACS. Full article

Background: Lipid-lowering therapies are an option for stabilizing lipid levels. Icosapent ethyl (IPE) is a highly purified formulation of eicosapentaenoic acid, which can reduce lipid action, improve plaque stabilization, reduce platelet aggregation, lower TG, and prevent cardiovascular events. IPE is frequently used with statins to manage elevated TG levels. However, the evidence on IPE as a lipid-lowering agent is limited, and no updated systematic review and meta-analysis have been published considering the recent advancements in the field and newly published studies. Therefore, we aim to fill this gap. Methods: We used the PRISMA guidelines and the PICO (Population, Intervention, Comparison, and Outcome) framework to conduct this review, aiming to answer the question, “Can IPE benefit patients at cardiovascular risk?” GRADE was used to evaluate evidence levels to adhere to the highest criteria. Results: Predominantly, the evaluated population presented TG levels between ≥135 mg/dL and 500 mg/dL and LDL-C levels between >40 mg/dL and ≤100 mg/dL. The included studies showed a reduction in TG and LDL-C and a decrease in cardiovascular events. It means that, according to our systematic review evidence analysis, IPE has been effective in lowering blood lipid levels, including TG, and reducing cardiovascular death and events, such as non-fatal stroke or hospitalization for unstable angina. However, it is worth noting that these results were primarily from patients undergoing statin therapy. According to our meta-analysis, IPE may not be considered a lipid-lowering drug, as limited action associated with its use was evident in the quantitative results. However, caution is necessary, as only two studies were suitable for inclusion due to the differing outcomes in the analyzed samples. Conclusions: Despite the quantitative synthesis, IPE possesses anti-inflammatory, anti-thrombotic, and anti-atherogenic properties, highly related to cardiovascular protection. Based on our included studies, IPE was considered a promising therapy for atherosclerotic cardiovascular disease in conjunction with other lipid-lowering therapies, particularly statins, for patients with extremely high TG levels. The limitations of the reviewed studies may include small sample sizes, varying outcomes, and a small duration of interventions. Future clinical trials with similar outcomes, sample sizes, and intervention durations must be designed, and updated meta-analyses must be published in the following years to fully assess the effects of IPE as a lipid-lowering and cardiovascular protector drug. Full article

Myocardial infarction (MI), including ST-elevation MI (STEMI) and non-ST-elevation MI (NSTEMI), has been the leading cause of hospitalization and death. Exosomes participate in many physiological and pathological processes and have important effects on cell communication and function. This study analyzed the proteomic characteristics of plasma exosomes with the discovery of exosomal differentially expressed proteins (DEPs) in MI patients. Proteomics technology was used to identify the plasma exosomal DEPs in 41 patients in STEMI, NSTEMI, unstable angina, and CONTROL groups, and 406 exosomal DEPs were discovered. Further, 36 selected exosomal DEPs were validated with parallel reaction monitoring (PRM) in a new cohort of STEMI, NSTEMI, and CONTROL groups, and 7 were successfully verified. There were three (F13A1, TSPAN33, and YWHAZ) in the STEMI group and six (F13A1, TSPAN33, ITGA2B, GP9, GP5, and PPIA) in the NSTEMI group, and all were down-regulated compared to the CONTROL group with high sensitivity and specificity in MI that may be developed as biomarkers for MI and may become possible therapeutic targets for MI. Bioinformatics analysis revealed that these seven exosomal DEPs are of great significance in the molecular mechanism of MI. Therefore, the present study has provided insights to further explore the pathological mechanism and possible therapeutic targets in MI. Full article

Background/Objectives: Previous studies have revealed the predictive potential of remnant cholesterol (RC) for acute coronary syndrome (ACS) occurrence in the general population. However, whether this association applies to patients with antineutrophil cytoplasmic antibody-associated vasculitis (AAV), in which a lipid paradox exists, remains unclear. We investigated whether RC levels at diagnosis could predict ACS occurrence during follow-up in patients with AAV. Methods: This study included 139 patients with AAV. ACS was defined as ST-elevation myocardial infarction (STEMI), non-STEMI, or unstable angina occurring after AAV diagnosis. RC levels were calculated as (total cholesterol)–(low-density lipoprotein cholesterol)–(high-density lipoprotein cholesterol). Patients were categorised into three groups by RC tertiles: highest (≥26.2 mg/dL), middle (19.1−26.1 mg/dL), and lowest (≤19.0 mg/dL) tertile groups. Results: The median age of the 139 patients (male, 31.7%) was 58.0 years. During follow-up, six, two, and one patients were diagnosed with ACS in the highest, middle, and lowest tertile groups, respectively. Patients in the highest tertile group exhibited a significantly lower ACS-free survival rate than those in the lowest tertile (p = 0.030). In the multivariable Cox hazards model, male sex (hazard ratio [HR] 9.054, 95% confidence interval [CI] 1.786−45.910), Birmingham vasculitis activity score (HR 1.147, 95% CI 1.033−1.274), and the highest tertile of RC levels (HR 10.818, 95% CI 1.867–62.689) were significantly and independently associated with ACS occurrence during follow-up in patients with AAV. Conclusions: Our findings indicate that RC levels at diagnosis may predict ACS occurrence during follow-up in patients with AAV, regardless of the traditional cardiovascular risk factors. Full article

Background: Lower socioeconomic status (SES) has been associated with increased mortality from coronary heart disease. This excess risk, relative to affluent patients, may be due to a combination of more adverse cardiovascular-risk factors, inequalities in access to cardiac investigations, longer waiting times for cardiac revascularisation and lower use of secondary prevention drugs. We sought to investigate whether socio-economic status influenced long-term all-cause mortality after PCI in a large metropolitan city (London), which serves a population of 11 million people with a mixed social background over a 10-year period. Methods: We conducted an observational cohort study of 123,780 consecutive PCI procedures from the Pan-London (United Kingdom) PCI registry. This data set is collected prospectively and includes all patients treated between January 2005 and December 2015. The database includes PCI performed for stable angina and ACS (ST-elevation myocardial infarction (STEMI), non-ST elevation myocardial infarction (NSTEMI), and unstable angina). Patient socio-economic status was defined by the English Index of Multiple Deprivation (IMD) score, according to residential postcode. Patients were analysed by quintile of IMD score (Q1, least deprived; Q5, most deprived). Median follow-up was 3.7 (IQR: 2.0–5.1) years and the primary outcome was all-cause mortality. Results: The mean age of the patients was 64.3 ± 12.1 years and 25.2% were female. A total of 22.4% of patients were diabetic and 27.3% had a history of previous myocardial infarction. The rates of long-term all-cause mortality increased progressively across quintiles of IMD score, with patients in Q5 showing significantly higher long-term mortality rates compared with patients in Q1 (p = 0.0044). This persisted following the inclusion of a propensity score in the proportional hazard model as a covariate (HR for Q5 compared to Q1: 1.15 [95% CI: 1.10–1.42]). Conclusions: This study has demonstrated that low SES is an independent predictor of adverse clinical outcomes following PCI in the large, diverse metropolitan city of London. There clearly are inequalities in cardio-vascular risk factors, time to access to medical treatment/PCI, access to complex imaging and devices during PCI, access to secondary prevention after PCI, and even race differences. Hence, attention to reducing the burden of cardiovascular risk factors and improving primary prevention, particularly in patients with lower SES, is required. Full article

Due to the routine use of endovascular revascularization and improved medical therapy, the majority of acute coronary syndrome (ACS) cases now have an uncomplicated course. However, in spite of the currently accepted secondary prevention standards, the residual risk of remote major adverse cardiovascular events (MACEs) after ACS remains high. Ultrasound carotid/subclavian atherosclerotic plaque assessment may represent an alternative approach to estimate the MACE risk after ACS and to control the quality of secondary prevention. Aim: To find the most important clinical predictors of MACEs in contemporary patients with predominantly uncomplicated ACS treated according to the Guidelines, and to study the potential of the longitudinal assessment of quantitative and qualitative ultrasound carotid/subclavian atherosclerotic plaque characteristics for MACE prediction after ACS. Methods: Patients with ACS, obstructive coronary artery disease (CAD) confirmed by coronary angiography, and carotid/subclavian atherosclerotic plaque (AP) who underwent interventional treatment were prospectively enrolled. The exclusion criteria were as follows: death or significant bleeding at the time of index hospitalization; left ventricular ejection fraction (EF) <30%; and statin intolerance. The clinical variables potentially affecting cardiovascular prognosis after ACS as well as the quantitative and qualitative AP characteristics at baseline and 6 months after the index hospitalization were studied as potential MACE predictors. Results: A total of 411 primary patients with predominantly uncomplicated ACS were included; AP was detected in 343 of them (83%). The follow-up period duration was 450 [269; 634] days. MACEs occurred in 38 patients (11.8%): seven—cardiac death, twenty-five—unstable angina/acute myocardial infarction, and six—acute ischemic stroke. In multivariate regression analyses, the most important baseline predictors of MACEs were diabetes (HR 2.22, 95% CI 1.08–4.57); the decrease in EF by every 5% from 60% (HR 1.22, 95% CI 1.03–1.46); the Charlson comorbidity index (HR 1.24, 95% CI 1.05–1.48); the non-prescription of beta-blockers at discharge (HR 3.24, 95% CI 1.32–7.97); and a baseline standardized AP gray scale median (GSM) < 81 (HR 2.06, 95% CI 1.02–4.19). Among the predictors assessed at 6 months, after adjustment for other variables, only ≥ 3 uncorrected risk factors and standardized AP GSM < 81 (cut-off value) at 6 months were significant (HR 3.11, 95% CI 1.17–8.25 and HR 3.77, 95% CI 1.43–9.92, respectively) (for all HRs above, all p-values < 0.05; HR and 95% CI values varied minimally across regression models). The baseline quantitative carotid/subclavian AP characteristics and their 6-month longitudinal changes were not associated with MACEs. All predictors retained significance after the internal validation of the models, and models based on the baseline predictors also demonstrated good calibration; the latter were used to create MACE risk calculators. Conclusions: In typical contemporary patients with uncomplicated interventionally treated ACS, diabetes, decreased EF, Charlson comorbidity index, non-prescription of beta-blockers at discharge, and three or more uncontrolled risk factors after 6 months were the most important clinical predictors of MACEs. We also demonstrated that a lower value of AP GSM reflecting the plaque vulnerability, measured at baseline and after 6 months, was associated with an increased MACE risk; this effect was independent of clinical predictors and risk factor control. According to our knowledge, this is the first demonstration of the independent role of longitudinal carotid/subclavian AP GSM assessment in MACE prediction after ACS. Full article

Background: In the study of coronary artery disease, the mechanisms underlying atherosclerosis initiation and progression or regression remain incompletely understood. Our research conceptualized the cardiovascular system as an integrated network of pumps and pipes, advocating for a paradigm shift from static imaging of coronary stenosis to dynamic assessments of coronary flow. Further review of fluid mechanics highlighted the water hammer phenomenon as a compelling analog for processes in coronary arteries. Methods: In this review, the analytical methodology employed a comprehensive, multifaceted approach that incorporated a review of fluid mechanics principles, in vitro acoustic experimentation, frame-by-frame visual angiographic assessments of in vivo coronary flow, and an artificial intelligence (AI) protocol designed to analyze the water hammer phenomenon within an acoustic framework. In the analysis of coronary flow, the angiograms were selected from patients with unstable angina if they had previously undergone one or more coronary angiograms, allowing for a longitudinal comparison of dynamic flow and phenomena. Results: The acoustic investigations pinpointed pockets of contrast concentrations, which might correspond to compression and rarefaction zones. Compression antinodes were correlated to severe stenosis, due to rapid shifts from low-pressure diastolic flow to high-pressure systolic surges, resulting in intimal injury. Rarefaction antinodes were correlated with milder lesions, due to de-escalating transitions from high systolic pressure to lower diastolic pressure. The areas of nodes remained without lesions. Based on the locations of antinodes and nodes, a coronary acoustic action map was constructed, enabling the identification of existing lesions, forecasting the progression of current lesions, and predicting the development of future lesions. Conclusions: The results suggested that intimal injury was likely induced by acoustic retrograde pressure waves from the water hammer phenomenon and developed new lesions at specifically exact locations. Full article

Background/Objectives: Vitamin K2 analogs are associated with decreased vascular calcification, which may provide protective benefits for individuals with coronary artery disease (CAD) by stimulating anti-calcific proteins like matrix Gla protein and adjusting innate immune responses. This study addresses a significant gap in understanding the association between serum levels of vitamin K2 analogs in different CAD types and examines their correlations with clinical risk parameters in CAD patients. Methods: This case–control study enrolled CAD patients and healthy controls to assess and compare serum concentrations of two vitamin K2 analogs including menaquinone-4 (MK-4) and menaquinone-7 (MK-7) via ultra-performance liquid chromatography with tandem mass spectrometry (UPLC-MS/MS). CAD risk factors were evaluated and related to serum levels of vitamin K2 analogs. The CAD group was further subdivided into stable angina, STEMI, NSTEMI, and unstable angina groups to investigate potential differences in vitamin K2 analog levels. Results: Patients experiencing acute coronary syndrome exhibited notably reduced serum levels of MK-4 and MK-7 (1.61 ± 0.66, and 1.64 ± 0.59 ng/mL, respectively) in comparison to the control group (2.29 ± 0.54, and 2.16 ± 0.46 ng/mL, respectively), with MK-4 and MK-7 displaying stronger associations with CAD risk indicators. Notable variations in vitamin K2 analog levels were found between CAD patients and control groups (p < 0.001). Unstable angina patients showed the lowest serum levels of MK-4 and MK-7. Conclusions: The present study demonstrated a higher prevalence rate of vitamin K2 deficiency among patients with CAD. The most pronounced decrease in MK-4 and MK-7 was observed in unstable angina patients. Moreover, these outcomes indicate the imperative requirement for an integrative approach that incorporates metabolic, lipid, and vitamin K2-related pathways in the risk stratification and management of CAD. Full article

Spontaneous coronary artery dissection is a rare cause of unstable angina, myocardial infarction, and sudden cardiac death, particularly among young women and individuals without conventional atherosclerotic risk factors. We present the case of a 43-year-old woman who had spontaneous coronary artery dissection involving the left main with extension to left anterior descending artery and left circumflex artery. She was ultimately managed medically, with a good outcome. Spontaneous coronary artery dissection is a unique and intricate condition that demands advanced diagnostic techniques and tailored management strategies. Greater awareness and advancements in imaging technologies have enhanced the detection and understanding of spontaneous coronary artery dissection. However, continued research is crucial to resolving outstanding uncertainties and optimizing patient outcomes. Full article

Cardiovascular disease continues to be a major contributor to global morbidity and mortality, with environmental and occupational factors such as air pollution, noise, and shift work increasingly recognized as potential contributors. Using a two-sample Mendelian randomization (MR) approach, this study investigates the causal relationships of these risk factors with the risks of unstable angina (UA) and myocardial infarction (MI). Leveraging single nucleotide polymorphisms (SNPs) as genetic instruments, a comprehensive MR study was used to assess the causal influence of four major air pollutants (PM_2.5, PM₁₀, NO₂, and NO_x), noise, and shift work on unstable angina and myocardial infarction. Summary statistics were derived from large genome-wide association studies (GWASs) from the UK Biobank and the FinnGen consortium (Helsinki, Finland), with replication using an independent GWAS data source for myocardial infarction. The inverse-variance weighted (IVW) approach demonstrated a significant positive correlation between shift work and the increased risk of both unstable angina (OR with 95% CI: 1.62 [1.12–2.33], p = 0.010) and myocardial infarction (OR with 95% CI: 1.46 [1.00–2.14], p = 0.052). MR-PRESSO analysis identified outliers, and after correction, the association between shift work and myocardial infarction strengthened (OR with 95% CI: 1.58 [1.11–2.27], p = 0.017). No notable causal associations were identified for air pollution or noise with either outcome. The replication of myocardial infarction findings using independent data supported a possible causal link between shift work and myocardial infarction (OR with 95% CI: 1.41 [1.08–1.84], p = 0.012). These results provide novel evidence supporting shift work as a likely causal risk factor for unstable angina and myocardial infarction, underscoring the need for targeted public health strategies to mitigate its cardiovascular impact. However, further investigation is necessary to elucidate the role of air pollution and noise in cardiovascular outcomes. Full article

Coronary artery disease (CAD) remains a major global health concern, significantly contributing to morbidity and mortality. This study aimed to investigate the co-occurrence patterns of diagnoses and comorbidities in CAD patients using a network-based approach. A retrospective analysis was conducted on 195 hospitalized CAD patients from a single hospital in Guangxi, China, with data collected on age, sex, and comorbidities. Network analysis, supported by sensitivity analysis, revealed key diagnostic clusters and comorbidity hubs, with hypertension emerging as the central node in the co-occurrence network. Unstable angina and myocardial infarction were identified as central diagnoses, frequently co-occurring with metabolic conditions such as diabetes. The results also highlighted significant age- and sex-specific differences in CAD diagnoses and comorbidities. Sensitivity analysis confirmed the robustness of the network structure and identified clusters, despite the limitations of sample size and data source. Modularity analysis uncovered distinct clusters, illustrating the complex interplay between cardiovascular and metabolic disorders. These findings provide valuable insights into the relationships between CAD and its comorbidities, emphasizing the importance of integrated, personalized management strategies. Future studies with larger, multi-center datasets and longitudinal designs are needed to validate these results and explore the temporal dynamics of CAD progression. Full article

Background: Despite existing evidence of the high predictive value of natriuretic peptides (NPs) in patients with heart failure (HF), patients treated with guideline-directed therapy who have low or near-normal NP levels are unlikely to be correctly stratified for risk of clinical outcomes. The aim of this study is to detect plausible predictors for poor one-year clinical outcomes in patients with HFpEF and low NT-proBNP treated with in accordance with conventional guidelines. Methods: A total of 337 patients with HF with preserved ejection fraction (HFpEF) who had low levels of N-terminal natriuretic pro-peptide (NT-proBNP) at discharge due to optimal guideline-based therapy were enrolled in the study. The course of the observation was 3 years. Echocardiography and the assessment of conventional hematological and biochemical parameters, including NT-proBNP, tumor necrosis factor-alpha, high-sensitivity C-reactive protein (hs-CRP), adropin, irisin, visfatin, and fetuin-A, were performed at baseline and at the end of the study. Results: Three-year cumulative clinical endpoints (cardiovascular death, myocardial infarction or unstable angina or acute coronary syndrome, worsening HF, sudden cardiac death, or cardiac-related surgery or all-cause death) were detected in 104 patients, whereas 233 did not meet the endpoint. After adjusting for an age ≥ 64 years and a presence of atrial fibrillation, diabetes mellitus, chronic kidney disease (CKD) stages 1–3 and dilated cardiomyopathy, the multivariable Cox regression analysis showed that an irisin level of ≤7.2 ng/mL was an independent predictor of cumulative clinical endpoint. Moreover, patients with levels of irisin > 7.2 ng/mL had a better Kaplan–Meier survival rate than those with a lower serum irisin level (≤7.2 ng/mL). Conclusions: Multivariable analysis showed that an age ≥ 64 years; the presence of atrial fibrillation, diabetes mellitus, CKD stages 1–3 and dilated cardiomyopathy; an LAVI ≥ 39 mL/m²; and serum levels of hs-CRP ≥ 6.10 mg/L, irisin ≤ 7.2 ng/mL, and visfatin ≤ 1.1 ng/mL were predictors of poor clinical outcomes in HFpEF with low levels of NT-proBNP. A serum level of irisin ≤ 7.2 ng/mL could emerge as valuable biomarker for predicting long-term prognosis among HFpEF patients with low or near-normal levels of NT-proBNP. Full article