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Recent studies reported that circulating microRNAs (miRNAs) can target different metalloproteases (MMPs) involved in matrix remodeling and plaque vulnerability. Consequently, they might have a role in the diagnosis and prognosis of coronary artery disease. To quantify circulating miRNAs (miRNA126, miRNA146, and miRNA21) suggested to have possible cardiovascular implications, as well as levels of MMP-1 and MMP-9, and to determine their association with left ventricular (LV) function and with arterial function, in patients with either ST-segment elevation acute myocardial infarction (STEMI) or stable ischemic heart disease (SIHD). A total of 90 patients with coronary artery disease (61% men, 58 ± 12 years), including 60 patients with STEMI and 30 patients with SIHD, were assessed within 24 h of admission, by measuring serum microRNAs, and serum MMP-1 and MMP-9. LV function was assessed by measuring ejection fraction (EF) by 2D and 3D echocardiography, and global longitudinal strain (GLS) by speckle tracking. Arterial function was assessed by echo tracking, CAVI, and peripheral Doppler. Circulating levels of miRNA146, miRNA21, and MMP1 were significantly increased in patients with STEMI vs. SIHD (p = 0.0001, p = 0.0001, p = 0.04, respectively). MiRNA126 negatively correlated with LVEF (r = −0.33, p = 0.01) and LV deformation parameters (r = −0.31, p = 0.03) in patients with STEMI and negatively correlated with ABI parameters (r = −0.39, p = 0.03, r = −0.40, p = 0.03, respectively) in patients with SIHD. MiRNA146 did not have any significant correlations, while higher values of miRNA21 were associated with lower values of GLS in STEMI patients and with higher values of GLS in SIHD patients. Both MMP1 and MMP9 correlated negatively with LVEF (r = −0.27, p = 0.04, r = −0.40, p = 0.001, respectively) and GLS in patients with STEMI, and positively with arterial stiffness in patients with SIHD (r = 0.40 and r = 0.32, respectively; both p < 0.05). MiRNA126, miRNA21, and both MMP1 and MMP9 are associated with LV and arterial function parameters in patients with acute coronary syndrome. Meanwhile, they inversely correlate with arterial function in patients with chronic atherosclerotic disease. However, further studies are needed to establish whether these novel biomarkers have diagnosis and prognosis significance.

Abstract Numerous diagnostic criteria for excessive trabeculation, or “noncompaction,” score the extent of the trabecular layer. Whether the trabeculations themselves have a poor or good contractility is largely unknown. We retrospectively analyzed cardiac magnetic resonance (CMR) of patients with excessive trabeculation of the left ventricle (LV). The LV was labeled into four regions: compact wall, central cavity (CC), trabeculations, and intertrabecular recesses (IR). For each label we calculated the systolic fractional volume change (SFVC) in short‐axis images (n = 15) and systolic fractional area change (SFAC) in four‐chamber images (n = 30). We measured the ejection fraction (EF) of IR, CC, and total cavity. Three methods to calculate EF of the total cavity were compared: trabeculations included (per guidelines), IR excluded (Jacquier criterion), and trabeculations contoured and excluded (contour‐EF). The SFVC and SFAC of the compact wall were similar with SFVC and SFAC of trabeculations. In contrast, the IR were more diminished in systole by comparison with the CC, having lower SFVC (39% vs. 56%) and SFAC (37% vs. 72%). EF of the IR was also greater than EF of the CC (61% vs. 44%). Excluding IR from the total cavity or including trabeculations negatively impacts the EF (44% and 40%, respectively, vs. 51% for contour‐EF). The trabecular layer operates at a high EF.

Muscle wasting is one of the main causes for exercise intolerance and ventilatory inefficiency in patients with heart failure and a strong predictor of frailty and reduced survival. The prevalence of sarcopenia is at least 20% in patients with heart failure. Patients with heart failure often have subclinical systemic inflammation, which may exert sustained effects on skeletal muscle. Besides exercise, nutrition should also be carefully evaluated as an appropriate diet with selected nutraceuticals may be able to stimulate muscle anabolism and inhibit muscle catabolism. This review summarizes the epidemiological and clinical trial evidence supporting the recommendations for the use of nutraceuticals with anti-inflammatory properties in heart failure and provides an overview of the state of the evidence for nutraceutical supplementation to prevent and/or mitigate heart failure muscle wasting.

BackgroundPatent foramen ovale (PFO) is a prevalent cardiac remnant of fetal anatomy that may pose a risk factor for stroke in some patients, while others can present with asymptomatic white matter (WM) lesions. The current study aimed to test the hypothesis that patients with a PFO who have a history of stroke or transient ischemic attack, compared to those without such a history, have a different burden and distribution of cerebral WM hyperintensities. Additionally, we tested the association between PFO morphological characteristics and severity of shunt, and their impact on the occurrence of ischemic cerebral vascular events and on the burden of cerebral WM lesions.Patients and methodsRetrospective, case–control study that included patients with PFO confirmed by transesophageal echocardiography. Right-to-left shunt size was assessed using transcranial Doppler ultrasound. Cerebral MRIs were analyzed for all participants using the semi-automated Quantib NDTM software for the objective quantification of WM lesions. WM lesions volume was compared between patients with and without a history of stroke. Additionally, the anatomical characteristics of PFOs were assessed to explore their relation to stroke occurrence and WM lesions volume.ResultsOf the initial 264 patients diagnosed with PFO, 67 met the inclusion criteria and were included in the analysis. Of them, 62% had a history of PFO-related stroke/TIA. Overall burden of WM lesions, including stroke volume, was not significantly different (p = 0.103). However, after excluding stroke volume, WM lesions volume was significantly higher in patients without stroke (0.27 cm3, IQR 0.03–0.60) compared to those with stroke/TIA (0.08 cm3, IQR 0.02–0.18), p = 0.019. Patients with a history of PFO-related stroke/TIA had a tendency to larger PFO sizes by comparison to those without, in terms of length and height, and exhibited greater right-to-left shunt volumes.DiscussionWe suggest that PFO may be associated with the development of two distinct cerebrovascular conditions (stroke and “silent” WM lesions), each characterized by unique imaging patterns. Further studies are needed to identify better the “at-risk” PFOs and gain deeper insights into their clinical implications.

Non-Alcoholic Fatty Liver Disease (NAFLD) is a common condition affecting around 10–25% of the general adult population, 15% of children, and even > 50% of individuals who have type 2 diabetes mellitus. It is a major cause of liver-related morbidity, and cardiovascular (CV) mortality is a common cause of death. In addition to being the initial step of irreversible alterations of the liver parenchyma causing cirrhosis, about 1/6 of those who develop NASH are at risk also developing CV disease (CVD). More recently the acronym MAFLD (Metabolic Associated Fatty Liver Disease) has been preferred by many European and US specialists, providing a clearer message on the metabolic etiology of the disease.The suggestions for the management of NAFLD are like those recommended by guidelines for CVD prevention. In this context, the general approach is to prescribe physical activity and dietary changes the effect weight loss. Lifestyle change in the NAFLD patient has been supplemented in some by the use of nutraceuticals, but the evidence based for these remains uncertain. The aim of this Position Paper was to summarize the clinical evidence relating to the effect of nutraceuticals on NAFLD-related parameters. Our reading of the data is that whilst many nutraceuticals have been studied in relation to NAFLD, none have sufficient evidence to recommend their routine use; robust trials are required to appropriately address efficacy and safety.

Tachycardia-induced cardiomyopathy (TIC) is characterized by reversible left ventricular (LV) dysfunction caused by long-standing tachycardia. The diagnosis of TIC is challenging due to lack of guidelines and specific assessment tools. Advanced imaging and endomyocardial biopsy should be taken into consideration in the future as contributors in the diagnostic process. There are numerous unknowns to TIC, the most pressing being the lack of diagnostic and prognostic tools. The presence of persistent negative LV remodeling after the normalization of the LV ejection fraction with adequate treatment of the tachycardia gives us a glimpse into the complex pathophysiologic processes at play, as well as the disease prognosis.

Cardiac amyloidosis (CA) still represents a frequently missed cause of heart failure with preserved ejection fraction (HFpEF). In the light of many new and effective therapies for immunoglobulin light chain amyloidosis (AL) and for transthyretin amyloidosis (ATTR), screening for amyloidosis as an important and potentially treatable diagnosis under the HFpEF becomes mandatory. A step-by-step algorithm for CA in HF patients was already provided by the guidelines. This review summarizes the role of all imaging modalities and biomarkers in the diagnosis and prognosis of both subtypes, the algorithm for diagnosis of CA, and new therapeutic options. It is the first Romanian publication which intends to bring altogether the current recommendations in the diagnosis and management of CA.

Valvular heart disease affects more that 100 million people worldwide. Valvular replacement remains the only definite treatment for most of the patients with severe disease. Careful medical management and periodic follow up of valve function is mandatory in order to prevent or diagnose prosthesis-related complications. We present a case of extensive mitral and aortic valve thrombosis and possible recurrent endocarditis in a 44-year-old woman non-adherent to anticoagulation therapy, presented with stroke. She also had a history of two mitral and aortic valvular heart replacement surgeries. Comprehensive and repeated imaging was used to evaluate and monitor the patient progression and outcome. Failure of adequate anticoagulation therapy to improve prosthesis function during hospitalization required third re-do surgery for mitral and aortic valve replacement with mechanical prosthesis.

Although acute myocarditis and coronary vasospasm are common differential diagnoses in the case of young patients with persistent ST elevation, the association of coronary vasospasm and acute fulminant myocarditis is a rare situation. We present the case of a 21 year-old male who presented with chest pain, ECG changes and biomarker levels initially interpreted as ST elevation myocardial infarction (STEMI), in which severe coronary vasospasm was identified. Shortly after, he developed cardiogenic shock and fulminant acute myocarditis was suspected.

Tachycardia-induced cardiomyopathy (TIC) is characterized by reversible left ventricular dysfunction caused by long-standing tachycardia. Treatment options for tachyarrhythmias causing TIC have evolved, especially the rhythm control strategies, ensuring a better and more sustainable control of the arrhythmia. We report the case of a 46-year-old male presenting with acute heart failure, atrial fibrillation (AF) of unknown duration and severe left ventricular dysfunction, as well as left ventricular dilation. His medical history was relevant for atrial flutter treated with catheter ablation, hypertension, and frequent atrial ectopy for which he had been prescribed amiodarone. Coronary artery disease and other potential causes for left ventricular dysfunction were excluded with coronary angiography and cardiac magnetic resonance. Thus, the patient had a high suspicion of TIC. We opted for a rhythm control strategy, however, after a successful initial electrical cardioversion, he had AF recurrence a few days later, under classic heart failure medication and antiarrhythmics. Pulmonary vein isolation was then performed, with no complications. At the one-month follow-up visit the patient was arrhythmia-free and had a normal left ventricular ejection fraction, with a slightly enlarged left ventricle. We opted to continue the heart failure medication. This case illustrates a typical case of AF induced TIC and the limited pharmacological options that exist for rhythm control, as well as the high efficacy of catheter ablation and value of imaging.

Introduction Heart failure (HF) with reduced ejection fraction is a complex condition requiring comprehensive diagnostic workup and management. Case presentation A 62-year-old male presented with resting HF and multiple syncopes. Medical history: former smoker, type 2 diabetes, advanced peripheral artery disease. Physical examination: congestive HF, obesity, discrete exophthalmia, grade 1 goitre, BP 110/70 mmHg, HR: 180 bpm. ECG: atrial fibrillation (AF), 180 bpm, RBBB, ST depression in anterolateral leads. CXR: pulmonary congestion, right pleural effusion. Blood analysis: D-dimer >5ng/ml, NTproBNP 12.900 pg/ml, hsTnI 550 ng/L, low TSH, fT3, fT4 4xULN. Cardiac echo: LVEF 20%, diffuse hypokinesis. HF symptom improvement with decongestion and rate control medication. Methimazole started on day 3. Intermittent conversion to sinus rhythm (SR) on day 7. ECG Holter (day 8-9): alternating moderate/high-rate AF and SR, 5-8 second sinus pauses and 1 syncope. LVEF 35% (day 9). Dual-chamber pacemaker implanted on day 10. Discharged on day 18. 2-months follow-up: LVEF 45%, NTproBNP 1.100 pg/ml, SR, HR 65-70 bpm, NYHA I HF. Conclusion Cardiac and non cardiac aggravating factors can contribute to HF worsening. Unmasking these factors is essential, as specific treatments can markedly improve the patient’s clinical status.

AL (light chain) amyloidosis is a life threatening disease. Untreated patients with involvement of the heart, a condition known as cardiac amyloidosis (CA), tend to have the most rapid disease progression and worst prognosis. Therefore, it is essential to early recognize the signs of symptoms of CA, and to identify the affected individuals with readily available non-invasive tests, as timely therapy can prolong life. Different imaging tests are used to diagnose and stratify the risk of the disease noninvasively, and to follow-up of the disease course and response to therapy. In this light, we present a case of a woman with cardiovascular risk factors, initially admitted for typical angina and decompensated heart failure (HF), who was later diagnosed with AL amyloidosis with cardiac involvement, by using multimodality imaging assessment in a step-by-step fashion. This changed completely the prognosis of the patient. Timely chemotherapy and stem cell transplantation led to an improvement in clinical status, biomarkers, and in a regression of amyloid myocardial infiltration showed by imaging.

The Coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), exhibits a wide spectrum of manifestations, from asymptomatic presentations to acute respiratory failure, myocardial injury, arterial or venous thrombosis, multiorgan failure, and death. Although COVID-19 mainly disrupts the respiratory syndrome, it has been shown to have detrimental impact on cardiac morphology and function, resulting in a broad range of cardiovascular complications and poor outcome, increasing morbidity and mortality of these patients. This review will summarize the knowledge on characterization of myocardial injury in COVID 19, by using cardiac biomarkers, electrocardiographic, and cardiac multi-modality imaging findings for an early and accurate diagnosis, proper management, correct treatment, and follow-up of COVID-19 patients.

Left ventricular non-compaction (LVNC) is an increasingly recognized phenotype. The current definition of the LVNC does not mention LV dysfunction as an absolute criterion in addition to morphological criteria. LV dilatation and decreased LV ejection fraction (LVEF) are often late manifestations of the disease and correlate with the occurrence of cardiovascular complications. However, to define LVNC as a cardiomyopathy, functional criteria must be fulfilled, in addition to the morphological ones. Multimodality imaging, such as myocardial deformation and myocardial work analysis derived from speckle tracking echocardiography (STE), in combination with cardiac magnetic resonance (CMR) might improve diagnosis and characterization of non-compaction, exposing earlier signs of LV systolic dysfunction. We present two comparative cases of LVNC in order to highlight the idea of subclinical dysfunction even in apparently benign forms with preserved LVEF, and also the importance of multimodality imaging approach.

Initially, the renal resistive index (RRI) was investigated with the aim of improving diagnosis in kidney diseases, but this goal was not met. Recently, many papers have highlighted the prognostic significance of the RRI in chronic kidney disease: specifically, in estimating the revascularization success of renal artery stenoses or the evolution of the graft and the recipients in renal transplantation. Moreover, the RRI has become significant in the prediction of acute kidney injury in critically ill patients. Studies in renal pathology have revealed correlations of this index with parameters of systemic circulation. The theoretical and experimental premises of this connection were then reconsidered, and studies analyzing the link between RRI and arterial stiffness, central and peripheral pressure, and left ventricular flow were conducted with this purpose. Many data currently indicate that RRI is influenced more by pulse pressure and vascular compliance than by renal vascular resistance—assuming that RRI reflects the complex interplay between systemic circulation and renal microcirculation and should be considered a marker of systemic cardiovascular risk beyond its prognostic relevance for kidney disease. In this review, we overview the clinical research that reveals the implications of RRI in renal and cardiovascular disease.

AimsNone of the conventional echocardiographic parameters alone predict increased NTproBNP level and symptoms, making diagnosis of heart failure with preserved ejection fraction (HFpEF) very difficult in some cases, in resting condition. We evaluated LA functions by 2D speckle tracking echocardiography (STE) on top of conventional parameters in HFpEF and preHF patients with diastolic dysfunction (DD), in order to establish the added value of the LA deformation parameters in the diagnosis of HFpEF.MethodsWe prospectively enrolled 125 patients, 88 with HFpEF (68±9 yrs), and 37 asymptomatic with similar risk factors with DD (preHF) (61±8 yrs). We evaluated them by NTproBNP, conventional DD parameters, and STE. Global longitudinal strain (GS) was added. LA reservoir (R), conduit (C), and pump function (CT) were assessed both by volumetric and STE. 2 reservoir strain (S) derived indices were also measured, stiffness (SI) and distensibility index (DI).ResultsLA R and CT functions were significantly reduced in HFpEF compared to preHF group (all pConclusionsBy adding LA functional analysis, we might improve the HFpEF diagnosis accuracy, compared to present guidelines. LA pump function is the only one able to differentiates preHF from HFpEF patients at rest. A value of SR_CT < -1.66/s outperformed conventional parameters from the scoring system, reservoir strain, and LA overload indices in HFpEF diagnosis. We suggest that LA function by STE could be incorporated in the current protocol for HFpEF diagnosis at rest as a major functional criterion, in order to improve diagnostic algorithm, and also in the follow-up of patients with risk factors and DD, as a prognostic marker. Future studies are needed to validate our findings.

Cardiotoxicity is an important side effect of vascular endothelial growth factor (VEGF) inhibitors therapy used in the treatment of various malignancies, leading to increased morbidity and mortality. Arterial hypertension, cardiac ischemia with the acceleration of atherosclerosis, arrhythmias, myocardial dysfunction and thromboembolic disease are the most feared cardiovascular adverse reactions due to VEGF inhibitors. Susceptibility for the occurrence of VEGF inhibitors-induced cardiotoxicity has multifactorial determinants, with a significant inter-individual variation. Baseline cardiovascular risk assessment of the patient, type and stage of cancer, dose and duration of VEGF inhibitors treatment and adjuvant chemotherapy or radiotherapy are the main predictors for cardiotoxicity. The role of the cardio-oncology team becomes essential for achieving maximum therapeutic anti-angiogenic effects with minimum cardiovascular side effects. This review will summarize the incidence, risk factors, mechanisms, management and treatment of VEGF inhibitors-induced cardiovascular toxicity.

The most common congenital cyanotic heart disease is described in the literature as the Tetralogy of Fallot. This abnormality is characterized by the presence of ventricular septal defect (VSD), obstruction of the right ventricular (RV) outflow tract, right ventricular hypertrophy, and overriding aorta. In patients with pulmonary atresia with ventricular septal defect (PA/VSD), major aortopulmonary collateral arteries (MAPCA) are common; however, although some of them do not have PA/VSD, they do have other particular anatomical variants. The case we are presenting in this article is a rare mild symptomatic adult noncorrected TOF, with preserved RV function, right aortic arch, and MAPCAs (“classic” thoracic MAPCAs but also abdominal MAPCAs). The anatomy of a complex congenital defect is well illustrated by cardiac magnetic resonance (CMR) and computer tomography angiography (CTA), and these imaging techniques are mostly used to understand the relative clinical “silence” TOF. Imaging scans thus play a key role in the evaluation of these patients, being very important to know the indications and limitations of each method, but also to learn to combine them with each other depending on the clinical picture of the patient’s presentation. Additionally, the close collaboration between clinicians and imagers is essential for a correct, complete and detailed preoperative evaluation, being subsequently essential for cardiovascular surgeons, the whole team thus deciding the best therapeutic management.

ObjectiveWe evaluated atrial fibrillation (AF) patients’ perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.MethodsThe RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30–45 and 150–210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.ResultsThe main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (p

Introduction and Objectives. Patients with dilated cardiomyopathy (DCM) and functional mitral regurgitation (FMR) present altered geometry and dynamics of the mitral annulus (MA). We aimed to further assess the relationship between the MA dysfunction, FMR severity, and LA dysfunction in patients with ischemic and nonischemic DCM by using three-dimensional transthoracic echocardiography (3DTTE). Methods. 56 patients (58 ± 17 years, 42 men) with DCM and FMR and 52 controls, prospectively enrolled, underwent 3DTTE dedicated for mitral valve (MV), LA, and left ventricle (LV) quantitative analysis. Results. Patients with FMR vs. controls presented increased MA size and sphericity during the entire systole, whereas MA fractional area change (MAFAC) and MA displacement were decreased (15 ± 5 vs. 28 ± 5%; and 5 ± 3 vs. 10 ± 2 mm, p

Heart failure (HF) is systemic and multiple organ syndrome, with metabolic insufficiency as one of its main causes. Heart metabolism disorders in HF activate other processes that futher worsens progression of the disease. Recent data shows that correction of energy metabolism in the heart by suppression of fatty acids (FA) oxydation and/or increase of glucose oxydation is one of promising approaches in HF patient’s treatment. Clinical studies showed that addition of trimetazidine to standard medication therapy improves sympthoms, cardiac function and prognosis in HF patients, not influencing negatively hemodynamics. The review is focused on rationale for and clinical benefits of trimetazidine application according to its influence on myocardial metabolism in HF. Also a very high level of preparedness of the drug to inclusion into main guidelines on HF is pointed on.

Two methods are currently available for left atrial (LA) strain measurement by speckle tracking echocardiography, with two different reference timings for starting the analysis: QRS (QRS-LASr) and P wave (P-LASr). The aim of MASCOT HIT study was to define which of the two was more reproducible, more feasible, and less time consuming. In 26 expert centers, LA strain was analyzed by two different echocardiographers (young vs senior) in a blinded fashion. The study population included: healthy subjects, patients with arterial hypertension or aortic stenosis (LA pressure overload, group 2) and patients with mitral regurgitation or heart failure (LA volume–pressure overload, group 3). Difference between the inter-correlation coefficient (ICC) by the two echocardiographers using the two techniques, feasibility and analysis time of both methods were analyzed. A total of 938 subjects were included: 309 controls, 333 patients in group 2, and 296 patients in group 3. The ICC was comparable between QRS-LASr (0.93) and P-LASr (0.90). The young echocardiographers calculated QRS-LASr in 90% of cases, the expert ones in 95%. The feasibility of P-LASr was 85% by young echocardiographers and 88% by senior ones. QRS-LASr young median time was 110 s (interquartile range, IR, 78-149) vs senior 110 s (IR 78-155); for P-LASr, 120 s (IR 80-165) and 120 s (IR 90-161), respectively. LA strain was feasible in the majority of patients with similar reproducibility for both methods. QRS complex guaranteed a slightly higher feasibility and a lower time wasting compared to the use of P wave as the reference.

BackgroundGreater understanding of differences between men and women with coronary heart disease is needed. Methods and ResultsIn this post hoc analysis of the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial, we described psychosocial factors, treatments, and outcomes of men versus women with stable coronary heart disease and explored the association of sex with psychosocial characteristics and cardiovascular risk. Cox proportional hazards models were used to assess the relationship between sex and outcomes. Interactions among sex, psychosocial factors, and the composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke were tested. Of 15 828 patients, 2967 (19%) were women. Among women, 21.2% felt often or always stressed at home (versus 9.8% of men), and 19.2% felt often or always sad or depressed (versus 10.1% of men; all P

BackgroundWe evaluated lipoprotein‐associated phospholipase A2 (Lp‐PLA2) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp‐PLA2 inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial. Methods and ResultsPlasma Lp‐PLA2 activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp‐PLA2 activity levels and outcomes. At baseline, the median Lp‐PLA2 level was 172.4 μmol/min per liter (interquartile range 143.1–204.2 μmol/min per liter). Comparing the highest and lowest Lp‐PLA2 quartile groups, the hazard ratios were 1.50 (95% CI 1.23–1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29–2.93) for hospitalization for heart failure, 1.42 (1.07–1.89) for cardiovascular death, and 1.37 (1.03–1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a ≈65% persistent reduction in median Lp‐PLA2 activity. There were no associations between on‐treatment Lp‐PLA2 activity or changes of Lp‐PLA2 activity and outcomes, and there were no significant interactions between baseline and on‐treatment Lp‐PLA2 activity or changes in Lp‐PLA2 activity levels and the effects of darapladib on outcomes. ConclusionsAlthough high Lp‐PLA2 activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp‐PLA2 activity by ≈65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp‐PLA2 activity. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00799903.