Takotsubo Syndrome and Gender Differences: Exploring Pathophysiological Mechanisms and Clinical Differences for a Personalized Approach in Patient Management.

Takotsubo syndrome (TTS), also known as the broken-heart syndrome, is a reversible condition typically observed in female patients presenting for acute coronary syndromes (ACS). Despite its increasing incidence, TTS often remains undiagnosed due to its overlap with ACS. The pathophysiology of TTS is complex and involves factors such as coronary vasospasm, microcirculatory dysfunction, increased catecholamine levels, and overactivity of the sympathetic nervous system. Diagnosing TTS requires a comprehensive approach, starting with clinical suspicion and progressing to both non-invasive and invasive multimodal tests guided by a specific diagnostic algorithm. Management of TTS should be personalized, considering potential complications, the presence or absence of coronary artery disease (CAD), diagnostic test results, and the patient's clinical course. The current data primarily derive from case series, retrospective analyses, prospective registries, and expert opinions. In recent years, there has been growing recognition of gender differences in the pathophysiology, presentation, and outcomes of TTS. This review provides an updated overview of gender disparities, highlighting the importance of tailored diagnostic and management strategies.

Aspirin in Primary Prevention: Looking for Those Who Enjoy It.

Based on a wealth of evidence, aspirin is one of the cornerstones of secondary prevention of cardiovascular disease. However, despite several studies showing efficacy also in primary prevention, an unopposed excess risk of bleeding leading to a very thin safety margin is evident in subjects without a clear acute cardiovascular event. Overall, the variability in recommendations from different scientific societies for aspirin use in primary prevention is a classic example of failure of simple risk stratification models based on competing risks (atherothrombosis vs. bleeding), perceived to be opposed but intertwined at the pathophysiological level. Notably, cardiovascular risk is dynamic in nature and cannot be accurately captured by scores, which do not always consider risk enhancers. Furthermore, the widespread use of other potent medications in primary prevention, such as lipid-lowering and anti-hypertensive drugs, might be reducing the benefit of aspirin in recent trials. Some authors, drawing from specific pathophysiological data, have suggested that specific subgroups might benefit more from aspirin. This includes patients with diabetes and those with obesity; sex-based differences are considered as well. Moreover, molecular analysis of platelet reactivity has been proposed. A beneficial effect of aspirin has also been demonstrated for the prevention of cancer, especially colorectal. This review explores evidence and controversies concerning the use of aspirin in primary prevention, considering new perspectives in order to provide a comprehensive individualized approach.

Muscle and joint function in the rotator cuff deficient shoulder.

Full-thickness rotator cuff tears can lead to poor coaptation of the humeral head to the glenoid, disrupting muscle forces required for glenohumeral joint stability, ultimately leading to joint subluxation. The aim of this study was to evaluate muscle forces and glenohumeral joint translations during elevation in the presence of isolated and combined full-thickness rotator cuff tears. Eight fresh-frozen upper limbs were mounted to a computer-controlled testing apparatus that simulated joint motion by simulated muscle force application. Scapular-plane abduction was performed, and glenohumeral joint translations were measured using an optoelectronic system. Testing was performed in the native shoulder, a following an isolated tear to the supraspinatus, as well as combined tears involving the supraspinatus and subscapularis, as well as supraspinatus, infraspinatus, and teres minor. Rotator cuff tears significantly increased middle deltoid force at 30°, 60°, and 90° of abduction relative to that in the native shoulder (p < 0.05). Significantly greater superior translations were observed relative to the intact shoulder due to combined tears to the supraspinatus and infraspinatus at 30° of abduction (mean increase: 1.6 mm, p = 0.020) and 60° of abduction (mean increase: 4.8 mm, p = 0.040). This study illustrates the infraspinatus-teres minor complex as a major humeral head depressor and contributor to glenohumeral joint stability. An increase in deltoid force during abduction occurs in the presence of rotator cuff tears, which exacerbates superior migration of the humeral head. The findings may help in the development of clinical tests in rotator cuff tear diagnostics, in surgical planning of rotator cuff repair, and in planning of targeted rehabilitation.

Eliminate LDL cholesterol after heart attack but only for a while.

There is a clear demonstration of the inverse linear correlation between LDL cholesterol levels and clinical benefit. However, the timing of the action of lipid-lowering drugs is not clear. According to animal studies with recombinant lipoprotein A-1, the composition of atherosclerosis changes within 40 h (with variations in lipid and inflammatory contents). Progression-regression studies of atherosclerosis in humans confirm the data, highlighting a rapid change in the plaque over 5 weeks. The data are also in line with what emerges from the survival curves of the old study comparing atorvastatin 80 mg vs. placebo (Myocardial Ischaemia Reduction with Aggressive Cholesterol Lowering). The spacing of the curves occurs after only 4 weeks, indicating the precociousness of the favourable effects of powerful statins. Finally, a recent Odyssey post hoc analysis compared the risk of cardiac death and coronary revascularization between a group in which alirocumab lowered LDL cholesterol to below 15 mg (Group 1 and in which the drug was therefore stopped) against the subjects in the placebo group (Group 2), applying a propensity score matching. The primary endpoint occurred in a lower percentage of patients in Group 1 (6.4 vs. 8.4%). Furthermore, patients in Group 1 had a significantly lower hazard ratio (HR) for major adverse cardiovascular events [0.72; 95% confidence interval (CI) 0.51-0.997; P = 0.047] compared with the entire alirocumab group vs. placebo (HR 0.85; 95% CI 0.78-0.93; P < 0.001). According to these preliminary observations, aggressive and early treatment of hypercholesterolaemia in subjects with acute coronary syndrome translates into improved clinical results compared with a strategy that provides for more gradual control. These data will need to be confirmed through further prospective clinical studies and ideally with early conducted atherosclerosis regression studies.

Controversy in cardiology: clopidogrel or acetylsalicylic acid in the treatment of chronic coronary syndromes?

Secondary prevention of patients with chronic coronary syndrome is based on the long-term use of a single anti-aggregating drug which is traditionally represented by acetylsalicylic acid (ASA) in light of the results of studies and meta-analyses which have demonstrated a clear anti-ischaemic efficacy against of an acceptable increase in the risk of bleeding, especially intracranial and gastrointestinal bleeding. The availability of drugs such as clopidogrel, which inhibits platelet activity through the P2Y12 receptor pathway, has called into question this paradigm, also in consideration of the fact that the scientific evidence that supports the use of ASA in secondary prevention is based on dated studies with some limitations. Over the last few years, randomized trials have demonstrated how clopidogrel has an efficacy profile comparable to that of ASA and a safety profile that is sometimes even better. In light of the new evidence, it is therefore legitimate to ask whether in this clinical scenario, ASA should still be considered the drug of choice or whether clopidogrel could represent the preferable alternative.

Intracoronary imaging to guide percutaneous coronary intervention: from evidence to guidelines.

Despite notable advances in devices and techniques, percutaneous coronary intervention (PCI) is still affected by a substantial number of complications and failure rates. Over the years, the use of intracoronary imaging (ICI) has dramatically improved the understanding of mechanical and technical factors related to successful and failed PCI, becoming a mainstay in complex trans-catheter interventions. However, ICI modalities are invasive, time-consuming, and costly, and a net clinical benefit needs to be shown in order to recommend their routine use in clinical practice. In the past, the lack of evidence from randomized trials has been reflected in the scepticism shown by international guidelines. The recent publication of large randomized clinical trials conducted worldwide has provided new evidence regarding the clinical usefulness of ICI guidance in PCI. The consistent reduction of adverse events achieved in these trials, also demonstrated in an updated meta-analysis, suggested that the use of ICI in PCI is compelling to achieve optimal technical results and better outcomes, especially in complex high-risk interventions. Also considering the burden of information provided by ICI on coronary artery disease, looking from the inside seems today an opportunity that modern cardiology cannot ignore anymore.

Subacromial contact after acromioplasty in the rotator cuff deficient shoulder.

Subacromial impingement (SAI) is associated with shoulder pain and dysfunction and is exacerbated by rotator cuff tears; however, the role of acromioplasty in mitigating subacromial contact in the rotator cuff deficient shoulder remains debated. This study aimed to quantify the influence of isolated and combined tears involving the supraspinatus on subacromial contact during abduction; and second, to evaluate the influence of acromioplasty on joint space size and subacromial contact under these pathological conditions. Eight fresh-frozen human cadaveric upper limbs were mounted to a computer-controlled testing apparatus that simulated joint motion by simulated force application. Shoulder abduction was performed while three-dimensional joint kinematics was measured using an optoelectronic system, and subacromial contact evaluated using a digital pressure sensor secured to the inferior acromion. Testing was performed after an isolated tear to the supraspinatus, as well as tears involving the subscapularis and infraspinatus-teres minor, both before and after acromioplasty. Rotator cuff tears significantly increased peak subacromial pressure (p < 0.001), average subacromial pressure (p = 0.001), and contact force (p = 0.034) relative to those in the intact shoulder. Following acromioplasty, significantly lower peak subacromial contact pressure, force and area were observed for all rotator cuff tears involving the supraspinatus at 30° of abduction (p < 0.05). Acromioplasty predominantly reduces acromion thickness anteriorly thereby reducing subacromial contact in the rotator cuff deficient shoulder, particularly in early to mid-abduction where superior glenohumeral joint shear force potential is large. These findings provide a biomechanical basis for acromioplasty as an intervention for SAI syndrome and as an adjunct to rotator cuff repairs.

Leptin as predictor of cardiovascular events and high platelet reactivity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Leptin is a hormone involved in the regulation of food intake. Previous studies suggested an interplay between leptin, platelet aggregation, and cardiovascular outcome but this issue was not investigated in vivo in patients treated with percutaneous coronary intervention (PCI). We designed a study to evaluate the possible relation between leptin, cardiovascular outcome, and platelet reactivity (PR) in patients undergoing PCI. METHODS: 155 PCI patients had preprocedural measurements of PR and leptin plasma levels. The latter were assessed by ELISA. Hyperleptinemia was defined as leptin levels ≥14 ng/ml. PR was evaluated by the VerifyNowP2Y12 assay and expressed as P2Y12 reaction units (PRU). Patients were divided into three groups based on PR values and defined as low (LPR), normal (NPR), and high (HPR). Patients were followed for up 8 years. The primary endpoint was the incidence of Major Acute Cardiac Events (MACE) at long-term follow-up according to leptin groups. Secondary endpoints were the evaluation of leptin levels according to PR groups and the incidence of periprocedural myocardial infarction (PMI) according to leptin groups. RESULTS: Long-term follow-up was completed in 140 patients. Patients with hyperleptinemia experienced a higher MACE rate than the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). These results remained unchanged after adjusting for Body Mass Index, hypertension, and gender. Leptin levels were significantly different among groups of PR (P = 0.047). Leptin levels were higher in the HPR group (12.61 ± 16.58 ng/ml) compared to the LPR group (7.83 ± 8.87 ng/ml, P = 0.044) and NPR group (7.04 ± 7.03 ng/ml, P = 0.01). The rate of PMI was higher in hyperleptinemia patients (15.1% vs. 6.5%, P = 0.22). CONCLUSIONS: This study suggests that high leptin levels are associated with a worse clinical outcome in patients undergoing PCI and with HPR. Further studies are needed to define better the pathophysiological pathways underlying this association.

Management of Residual Risk in Chronic Coronary Syndromes. Clinical Pathways for a Quality-Based Secondary Prevention.

Chronic coronary syndrome (CCS), which encompasses a broad spectrum of clinical presentations of coronary artery disease (CAD), is the leading cause of morbidity and mortality worldwide. Recent guidelines for the management of CCS emphasize the dynamic nature of the CAD process, replacing the term "stable" with "chronic", as this disease is never truly "stable". Despite significant advances in the treatment of CAD, patients with CCS remain at an elevated risk of major cardiovascular events (MACE) due to the so-called residual cardiovascular risk. Several pathogenetic pathways (thrombotic, inflammatory, metabolic, and procedural) may distinctly contribute to the residual risk in individual patients and represent a potential target for newer preventive treatments. Identifying the level and type of residual cardiovascular risk is essential for selecting the most appropriate diagnostic tests and follow-up procedures. In addition, new management strategies and healthcare models could further support available treatments and lead to important prognostic benefits. This review aims to provide an overview of the diagnostic and therapeutic challenges in the management of patients with CCS and to promote more effective multidisciplinary care.

[ANMCO Position paper: Colchicine as a therapeutic agent in coronary syndromes]. / Position paper ANMCO: La colchicina come agente terapeutico nelle sindromi coronariche.

With the growing knowledge about the role of inflammatory processes in the pathogenesis of atherosclerotic lesions, inflammation has been identified as a cardiovascular risk factor and therapeutic target to reduce the residual risk in patients with atherosclerotic disease. Several therapeutic agents with anti-inflammatory action have been tested to evaluate their efficacy and safety in the context of atherosclerotic cardiovascular diseases. Among these, colchicine, a drug with multiple therapeutic effects including anti-inflammatory action, in randomized clinical trials conducted in the setting of atherosclerotic cardiovascular disease secondary prevention, significantly reduced the risk of adverse cardiovascular events.This position paper of the Italian Association of Hospital Cardiologists (ANMCO) summarizes the main biological mechanisms through which colchicine contributes to the inhibition of inflammatory processes that increase the atherosclerotic cardiovascular risk. Furthermore, the document reports the available evidence on clinical impact of colchicine treatment in the reduction of residual cardiovascular risk in chronic and acute coronary syndromes. Finally, practical information is provided regarding the use of this drug in this specific clinical setting, emphasizing precautions and possible side effects.

Clinical impact of OCT-derived suboptimal stent implantation parameters and definitions.

AIMS: Despite growing evidence supporting the clinical utility of optical coherence tomography (OCT) guidance during percutaneous coronary interventions (PCIs), there is no common agreement as to the optimal stent implantation parameters that enhance clinical outcome. METHODS AND RESULTS: We retrospectively examined the predictive accuracy of suboptimal stent implantation definitions proposed from the CLI-OPCI II, ILUMIEN-IV OPTIMAL PCI, and FORZA studies for the long-term risk of device-oriented cardiovascular events (DoCE) in the population of large all-comers CLI-OPCI project. A total of 1020 patients undergoing OCT-guided drug-eluting stent implantation in the CLI-OPCI registry with a median follow-up of 809 (quartiles 414-1376) days constituted the study population. According to CLI-OPCI II, ILUMIEN-IV OPTIMAL PCI, and FORZA criteria, the incidence of suboptimal stent implantation was 31.8%, 58.1%, and 57.8%, respectively. By multivariable Cox analysis, suboptimal stent implantation criteria from the CLI-OPCI II [hazard ratio 2.75 (95% confidence interval 1.88-4.02), P < 0.001] and ILUMIEN-IV OPTIMAL PCI [1.79 (1.18-2.71), P = 0.006] studies, but not FORZA trial [1.11 (0.75-1.63), P = 0.597], were predictive of DoCE. At long-term follow-up, stent edge disease with minimum lumen area <4.5 mm2 [8.17 (5.32-12.53), P < 0.001], stent edge dissection [2.38 (1.33-4.27), P = 0.004], and minimum stent area <4.5 mm2 [1.68 (1.13-2.51), P = 0.011] were the main OCT predictors of DoCE. CONCLUSION: The clinical utility of OCT-guided PCI might depend on the metrics adopted to define suboptimal stent implantation. Uncovered disease at the stent border, stent edge dissection, and minimum stent area <4.5 mm2 were the strongest OCT associates of stent failure.

Effects of Lipid Lowering Therapies on Vulnerable Plaque Features: An Updated Narrative Review of the Literature.

The clinical evidence on the efficacy of lipid lowering therapy in patients with coronary artery disease (CAD) is unequivocally established. However, the effects of these therapies on plaque composition and stability are less clear. The use of intracoronary imaging (ICI) technologies has emerged as a complement to conventional angiography to further characterize plaque morphology and detect high-risk plaque features related to cardiovascular events. Along with clinical outcomes studies, parallel imaging trials employing serial evaluations with intravascular ultrasound (IVUS) have shown that pharmacological treatment has the capacity to either slow disease progression or promote plaque regression, depending on the degree of lipid lowering achieved. Subsequently, the introduction of high-intensity lipid lowering therapy led to much lower levels of low-density lipoprotein cholesterol (LDL-C) levels than achieved in the past, resulting in greater clinical benefit. However, the degree of atheroma regression showed in concomitant imaging trials appeared more modest as compared to the magnitude of clinical benefit accrued from high-intensity statin therapy. Recently, new randomized trials have investigated the additional effects of achieving very low levels of LDL-C on high-risk plaque features-such as fibrous cap thickness and large lipid accumulation-beyond its size. This paper provides an overview of the currently available evidence of the effects of moderate to high-intensity lipid lowering therapy on high-risk plaque features as assessed by different ICI modalities, reviews data supporting the use of these trials, and analyse the future perspectives in this field.

The temptation of anticoagulant therapy after transcatheter aortic valve implantation.

The choice of the best antithrombotic strategy after transcatheter aortic valve implantation (TAVI) must be based on the careful balance between the ischaemic risk and the bleeding risk and on the evaluation of some concomitant conditions, such as atrial fibrillation or coronary artery disease which may lead to the choice of anticoagulant treatment or antiplatelet therapy. Another element to consider is the possibility, albeit remote in post-TAVI patients, of thrombosis of the valve leaflets, an event whose clinical impact has yet to be fully clarified and which however appears to present a lower incidence in patients treated with anticoagulants. Recent evidence has shown that in patients who do not require anticoagulant therapy, single therapy with aspirin represents the best treatment compared to dual antiplatelet or to the addition of anticoagulant which in post-TAVI patients should be reserved only for those with a clear indication such as atrial fibrillation. It is still much debated whether in this case the choice should fall on vitamin K antagonists or on the new direct-acting anticoagulants, as the comparison studies have produced inconclusive results.

Sex-specific features of optical coherence tomography detected plaque vulnerability related to clinical outcomes: insights from the CLIMA study.

PURPOSE: To investigate the different impact of optical coherence tomography (OCT)-derived vulnerable plaque features on future adverse events (AEs) according to the biological sex. METHODS: The prospective multicenter CLIMA study (ClinicalTrials.gov: NCT02883088) enrolled 1003 patients with OCT plaque analysis of non-treated coronary plaques located in the proximal left anterior descending artery. Sex-specific differences in plaque composition and vulnerable features were described. We investigated the incidence of AEs, including cardiac death, any myocardial infarction and target vessel revascularization at 1-year. RESULTS: Among 1003 patients, 24.6% were women. Women were older and more frequently affected by chronic kidney disease. Dyslipidemia, prior MI and smoking habit were more common in men. At OCT analysis, women had shorter plaque length (p < 0.001), ticker fibrous cap (p = 0.001), smaller maximum lipid arc (p = 0.019), lower macrophage infiltration (p < 0.001) and intra-plaque layered tissue (p = 0.007). During follow-up, 65 AEs were registered. The presence of a thin fibrous cap and a large macrophage infiltration (> 67°) predicted AEs in both sexes. The presence of macrophages (HR 3.38, p = 0.018) and a small minimum lumen area (HR 4.97, p = 0.002) were associated with AEs in women but not in men, while a large lipid arc (> 180°) was associated with AEs in men (HR 2.56, p = 0.003) but not in women. CONCLUSION: This subanalysis of the CLIMA study investigated for the first-time sex-specific OCT features of plaque vulnerability associated with AEs. Local inflammation was associated with AEs in women and a large lipid arc was predictive in men. OCT may help develop sex-specific risk stratification strategies.

Comparison between different approaches to evaluate fibrous cap thickness in sequential optical coherence tomography studies.

BACKGROUND: In this in-vivo human study we tested the reproducibility for optical coherence tomography (OCT) assessment of lumen area (LA) and plaque components measurements, such as lipid arc extension and fibrous cap thickness (FCt). METHODS: We tested the variability of LA, lipid arc and FCt assessments in two repeated OCT pullbacks from the same diseased coronary segment matched using fiduciary anatomical landmarks. In particular, for the reliability of minimal FCt measurement we compared four different approaches based on continuous (longitudinal) or segmental (spot) individuation of smaller thickness: 1) comparison of single minimal FCt individuated alongside all plaque extension in the two pullbacks (Longitudinal (L)-spot minimal FCt value); 2) comparison of the mean FCt values of the plaque in the two pullbacks (L-plot mean FCt value); 3) comparison between the single minimal FCt value obtained in the first pullback and the single FCt obtained in the matched CS of second pullback (L-spot CS matched FCt value); 4) comparison of measurements obtained by visual selection of CS with minimal FCt s in the two pullbacks (single-spot minimal FCt value). RESULTS: From the paired analyses of 20 non culprit lesions (accounting for a total of 387 matched CS), we found a suboptimal in-segment correlation for LA (Intra-Class Coefficient [ICC] 0.731), but a good in-segment correlation for lipid arc (ICC 0.963). Regarding FCt measurement, a high reproducibility was obtained applying continuous assessment; in particular, the best correlation was observed with L-spot minimal FCt value and the L-plot mean FCt (ICC 0.893 and 0.952, respectively) with small inter-pullback differences (confidence intervals less than 0.04 mm). CONCLUSIONS: In this methodological study we observed a good reproducibility for quantitative plaque measurements with OCT confirming its reliability for serial assessment. In particular, longitudinal measurement in multiple adjacent frames seems to be the more accurate and reproducible approach for sequential FCt assessment.

[From regression to stabilization: new insights into the evolution of coronary atherosclerotic plaque]. / Dalla regressione alla stabilizzazione: l'evoluzione della placca aterosclerotica coronarica secondo le nuove evidenze.

Coronary artery atherosclerosis is a constantly evolving disease. Over the years, new drug therapies have been shown to reduce adverse cardiovascular events and improve the survival of patients with coronary artery disease. New intracoronary imaging modalities, including intravascular ultrasound, optical coherence tomography, and near-infrared spectroscopy, have been introduced to detect the anatomic changes which follow an effective lipid-lowering therapy in human coronary plaques. Particularly, the use of optical coherence tomography made it possible to evaluate plaque composition and showed how an intensive lipid-lowering therapy can stabilize atherosclerosis by improving vulnerable plaque features. Future non-invasive applications are required for large-scale use of these findings.

Definition of Optimal Optical Coherence Tomography-Based Stent Expansion Criteria: In-Stent Minimum Lumen Area Versus Residual Stent Underexpansion.

BACKGROUND: The mismatch between in-stent minimum lumen area (sMLA) and reference vessel lumen area, defined as stent underexpansion (SU), could be an important determinant of stent failure. We tested the clinical predictive value of absolute sMLA in comparison to relative SU in the context of the CLI-OPCI (Centro Per La Lotta Contro L'Infarto-Optimisation of Percutaneous Coronary Intervention) project registry. METHODS: We retrospectively analyzed end procedural optical coherence tomography findings in 1211 patients (1422 lesions) undergoing percutaneous coronary intervention, assessing the prevalence and magnitude of residual SU and exploring correlation with outcome in comparison with sMLA. RESULTS: In our series, both sMLA and SU were related to vessel size and anatomic lesion complexity. When compared with patients without adverse event at follow-up, those experiencing device-oriented cardiovascular events (composite of cardiac death, target vessel myocardial infarction, target lesion revascularization, and stent thrombosis) showed a lower sMLA (5.6±2.1 versus 6.1±2.1 mm2; P=0.011) but a comparable degree of SU (11.6±14.1% versus 11.2±13.3%; P=0.734). The prespecified cutoff value of sMLA <4.5 mm2, documented in 23.8% of cases, was confirmed as independent outcome predictor for device-oriented cardiovascular events (hazard ratio [HR], 2.05 [95% CI, 1.5-2.9]) including target lesion revascularization (HR, 2.43 [95% CI, 1.7-3.5]) and stent thrombosis (HR, 3.23 [95% CI, 1.7-6.3]). A residual SU of 10%, 20%, and 30% was observed in 38.0%, 18.2%, and 7.6% of cases, respectively. No grade of residual SU significantly increased the risk of stent failure, unless if an SU >20% was associated with an sMLA <4.5 mm2 (HR, 3.11 [95% CI, 1.7-5.6]). Finally, an association between stent overexpansion (ie, >110%) and device-oriented cardiovascular events was also observed (HR, 1.60 [95% CI, 1.1-2.3]). CONCLUSIONS: Final absolute sMLA and not relative SU was associated with an increased risk of stent failure. A variable grade of SU was common, but it resulted in being clinically relevant only when associated with an sMLA <4.5 mm2.

The Role of the Association Between Serum C-Reactive Protein Levels and Coronary Plaque Macrophage Accumulation in Predicting Clinical Events - Results from the CLIMA Registry.

The present investigation aims to study the interaction between systemic and intra-plaque inflammation in predicting cardiac events. We investigated C-reactive protein (CRP) levels as well as plaque inflammation with optical coherence tomography (OCT)-detected macrophages in the CLIMA study. 689 patients had admission CRP serum values reported, and high CRP values were defined as ≥ 2 mg/dl. The main study endpoint was a composite of cardiac death, myocardial infarction, and/or target vessel revascularization at 1-year follow-up. At multivariate Cox regression analysis, a large (hazard ratio [HR] 2.27, 95% confidence interval [CI] 1.2-4.3; p = 0.013) and superficial (HR 2.78, 95%CI 1.5-5.1; p = 0.001) macrophage arc was predicted of the main composite endpoint in patients with high CRP levels. Patients with large/superficial macrophage accumulation and low CRP levels were not at higher risk of adverse events. The presence of high CRP levels and large/superficial macrophage accumulation at OCT analysis identified patients at higher risk of clinical events.