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Background: The 2018 cholesterol guidelines of the American Heart Association and the American College of Cardiology (AHA/ACC) changed 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) eligibility criteria for primary prevention to include multiple risk enhancers and novel intensive lipid-lowering therapies for secondary prevention.Objectives: This study sought to determine how guideline changes affected identification for preventive therapy in young adults with premature myocardial infarction (MI).Methods: The study identified adults presenting with first MI at Duke University Medical Center in Durham, North Carolina. Statin therapy eligibility was determined using the 2013 ACC/AHA and 2018 AHA/ACC guidelines criteria. The study also determined potential eligibility for intensive lipid-lowering therapies (very high risk) under the 2018 AHA/ACC guidelines, by assessing the composite of all-cause death, recurrent MI, or stroke rates in adults considered "very high risk" versus not.Results: Among 6,639 patients with MI, 41% were <55 years of age ("younger"), 35% were 55 to 65 years of age ("middle-aged"), and 24% were 66 to 75 years of age ("older"). Younger adults were more frequently smokers (52% vs. 38% vs. 22%, respectively) and obese (42% vs. 34% vs. 31%, respectively), with metabolic syndrome (21% vs. 19% vs. 17%, respectively) and higher low-density lipoprotein cholesterol (117 vs. 107 vs. 103 mg/dl, respectively) (p trend <0.01 for all). Pre-MI, fewer younger adults met guideline indications for 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitor (statin) therapy than middle-aged and older adults. The 2018 guideline identified fewer younger adults eligible for statin therapy at the time of their MI than the 2013 guideline (46.4% vs. 56.7%; p < 0.01). Younger patients less frequently met very high-risk criteria for intensive secondary prevention lipid-lowering therapy (28.3% vs. 40.0% vs. 81.4%, respectively; p < 0.01). Over a median 8 years of follow-up, very high-risk criteria were associated with increased risk of major adverse cardiovascular events in individuals <55 years of age (hazard ratio: 2.09; 95% confidence interval: 1.82 to 2.41; p < 0.001), as was the case in older age groups (p interaction = 0.54).Conclusions: Most younger patients with premature MI are not identified as statin candidates before their event on the basis of the 2018 guidelines, and most patients with premature MI are not recommended for intensive post-MI lipid management. [ABSTRACT FROM AUTHOR]

Background: In the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, patients with atrial fibrillation and ≥2 dose-adjustment criteria (age ≥80 years, weight ≤60 kg, or creatinine ≥1.5 mg/dl [133 μmol/l]) were randomized to receive apixaban 2.5 mg twice daily or warfarin.Objectives: The purpose of this study was to describe the effects of apixaban dose adjustment on clinical and pharmacological outcomes.Methods: Patients receiving the correct dose of study drug were included (n = 18,073). The effect of apixaban 2.5 mg twice daily versus warfarin on population pharmacokinetics, D-dimer, prothrombin fragment 1 + 2 (PF1+2), and clinical outcomes was compared with the standard dose (5 mg twice daily).Results: Patients receiving apixaban 2.5 mg twice daily exhibited lower apixaban exposure (median area under the concentration time curve at a steady state 2,720 ng/ml vs. 3,599 ng/ml; p < 0.0001) than those receiving the standard dose. In patients with ≥2 dose-adjustment criteria, reductions in D-dimers (p interaction = 0.20) and PF1+2 (p interaction = 0.55) were consistent with those observed in the standard-dose population. Patients with ≥2 dose-adjustment criteria (n = 751) were at higher risk for stroke/systemic embolism, major bleeding, and all-cause death than the standard-dose population (0 or 1 dose-adjustment criterion, n = 17,322). The effect of apixaban 2.5 mg twice daily versus warfarin in the ≥2 dose-adjustment criteria population was consistent with the standard dose in the reductions in stroke or systemic embolism (p interaction = 0.26), major bleeding (p interaction = 0.25), and death (p interaction = 0.72).Conclusions: Apixaban drug concentrations were lower in patients receiving 2.5 mg twice daily compared with 5 mg twice daily. However, the effects of apixaban dose adjustment to 2.5 mg versus warfarin were consistent for coagulation biomarkers and clinical outcomes, providing reassuring data on efficacy and safety. (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation [ARISTOTLE]; NCT00412984). [ABSTRACT FROM AUTHOR]

Background: The long-term evolution of premature coronary artery disease (CAD) is unknown.Objectives: The objective of this study was to describe the evolution of coronary atherosclerosis in young patients and identify the risk factors of poor outcomes.Methods: Participants age ≤45 years with acute or stable obstructive CAD were prospectively enrolled and followed. The primary endpoint was all-cause death, myocardial infarction (MI), refractory angina requiring coronary revascularization, and ischemic stroke.Results: Eight hundred-eighty patients with premature CAD were included. They were age 40.1 ± 5.7 years, mainly men, smokers, with a family history of CAD or hypercholesterolemia. At baseline presentation, 91.2% underwent coronary revascularization, predominantly for acute MI (78.8%). Over a follow-up of 20 years, one-third (n = 264) of patients presented with a total of 399 ischemic events, and 36% had at least a second recurrent event. MI was the most frequent first recurrent event (n = 131 of 264), mostly related to new coronary lesions (17.3% vs. 7.8%; p = 0.01; hazard ratio [HR]:1.45; 95% confidence interval [CI]: 1.09 to 1.93 for new vs. initial culprit lesion). All-cause death (n = 55; 6.3%) occurred at 8.4 years (median time). Ethnic origin (sub-Saharan African vs. Caucasian, adjusted hazard ratio [adjHR]: 1.95; 95% CI: 1.13 to 3.35; p = 0.02), inflammatory disease (adjHR: 1.58; 95% CI: 1.05 to 2.36; p = 0.03), and persistent smoking (adjHR: 2.32; 95% CI: 1.63 to 3.28; p < 0.01) were the strongest correlates of a first recurrent event. When considering all recurrent events, the same factors and Asian ethnicity predicted poor outcome, but persistent smoking had the greatest impact on prognosis.Conclusions: Premature CAD is an aggressive disease despite the currently recommended prevention measures, with high rates of recurrent events and mortality. Ethnicity and concomitant inflammatory disease are associated with poor prognoses, along with insufficient control of risk factors. [ABSTRACT FROM AUTHOR]

Background: Inhibition of the interleukin (IL)-1β innate immunity pathway is associated with anti-inflammatory effects and a reduced risk of recurrent cardiovascular events in stable patients with previous myocardial infarction (MI) and elevated high-sensitivity C-reactive protein (hs-CRP).Objectives: This study assessed the association between IL-1β level with all-cause mortality in patients with acute ST-segment elevation MI who underwent primary percutaneous coronary intervention and the interplay between IL-1β and hs-CRP concentrations on the risk of premature death.Methods: IL-1β concentration was measured in 1,398 patients with ST-segment elevation MI who enrolled in a prospective cohort. Crude and hazard ratios for all-cause and cardiovascular mortality were analyzed at 90 days and 1 year using multivariate Cox proportional regression analysis. Major adverse cardiovascular events (MACEs) were analyzed.Results: IL-1β concentration measured at admission was associated with all-cause mortality at 90 days (adjusted hazard ratio [adjHR]: 1.47 per 1 SD increase; 95% confidence interval [CI]: 1.16 to 1.87; p < 0.002). The relation was nonlinear, and the highest tertile of IL-1β was associated with higher mortality rates at 90 days (adjHR: 2.78; 95% CI: 1.61 to 4.79; p = 0.0002) and at 1 year (adjHR: 1.93; 95% CI: 1.21 to 3.06; p = 0.005), regardless of the hs-CRP concentration. Significant relationships were equally observed when considering cardiovascular mortality and MACEs at 90 days (adjHR: 2.42; 95% CI: 1.36 to 4.28; p = 0.002, and adjHR: 2.29; 95% CI: 1.31 to 4.01; p = 0.004, respectively) and at 1 year (adjHR: 2.32; 95% CI: 1.36 to 3.97; p = 0.002, and adjHR: 2.35; 95% CI: 1.39 to 3.96; p = 0.001, respectively).Conclusions: IL-1β measured at admission in patients with acute MI was independently associated with the risk of mortality and recurrent MACEs. [ABSTRACT FROM AUTHOR]

Background: In hemodynamically stable patients, complete revascularization (CR) following percutaneous coronary intervention (PCI) is associated with a better prognosis in chronic and acute coronary syndromes.Objectives: This study sought to assess the extent, severity, and prognostic value of remaining coronary stenoses following PCI, by using the residual SYNTAX score (rSS), in patients with cardiogenic shock (CS) related to myocardial infarction (MI).Methods: The CULPRIT-SHOCK (Culprit Lesion Only Percutaneous Coronary Intervention [PCI] Versus Multivessel PCI in Cardiogenic Shock) trial compared a multivessel PCI (MV-PCI) strategy with a culprit lesion-only PCI (CLO-PCI) strategy in patients with multivessel coronary artery disease who presented with MI-related CS. The rSS was assessed by a central core laboratory. The study group was divided in 4 subgroups according to tertiles of rSS of the participants, thereby isolating patients with an rSS of 0 (CR). The predictive value of rSS for the 30-day primary endpoint (mortality or severe renal failure) and for 30-day and 1-year mortality was assessed using multivariate logistic regression.Results: Among the 587 patients with an rSS available, the median rSS was 9.0 (interquartile range: 3.0 to 17.0); 102 (17.4%), 100 (17.0%), 196 (33.4%), and 189 (32.2%) patients had rSS = 0, 0 < rSS ≤5, 5 < rSS ≤14, and rSS >14, respectively. CR was achieved in 75 (25.2%; 95% confidence interval [CI]: 20.3% to 30.5%) and 27 (9.3%; 95% CI: 6.2% to 13.3%) of patients treated using the MV-PCI and CLO-PCI strategies, respectively. After multiple adjustments, rSS was independently associated with 30-day mortality (adjusted odds ratio per 10 units: 1.49; 95% CI: 1.11 to 2.01) and 1-year mortality (adjusted odds ratio per 10 units: 1.52; 95% CI: 1.11 to 2.07).Conclusions: Among patients with multivessel disease and MI-related CS, CR is achieved only in one-fourth of the patients treated using an MV-PCI strategy. and the residual SYNTAX score is independently associated with early and late mortality. [ABSTRACT FROM AUTHOR]

Background: Contemporary data are lacking regarding the prognosis and management of left ventricular thrombus (LVT).Objectives: The purpose of this study was to quantify the effect of anticoagulation therapy on LVT evolution using sequential imaging and to determine the impact of LVT regression on the incidence of thromboembolism, bleeding, and mortality.Methods: From January 2011 to January 2018, a comprehensive computerized search of LVT was conducted using 90,065 consecutive echocardiogram reports. Only patients with a confirmed LVT were included after imaging review by 2 independent experts. Major adverse cardiovascular events (MACE), which included death, stroke, myocardial infarction, or acute peripheral artery emboli, were determined as well as major bleeding events (BARC ≥3) and all-cause mortality rates.Results: There were 159 patients with a confirmed LVT. Patients were treated with vitamin K antagonists (48.4%), parenteral heparins (27.7%), and direct oral anticoagulants (22.6%). Antiplatelet therapy was used in 67.9% of the population. A reduction of the LVT area from baseline was observed in 121 patients (76.1%), and total LVT regression occurred in 99 patients (62.3%) within a median time of 103 days (interquartile range: 32 to 392 days). The independent correlates of LVT regression were a nonischemic cardiomyopathy (hazard ratio [HR]: 2.74; 95% confidence interval [CI]: 1.43 to 5.26; p = 0.002) and a smaller baseline thrombus area (HR: 0.66; 95% CI: 0.45 to 0.96; p = 0.031). The frequency of MACE was 37.1%; mortality 18.9%; stroke 13.3%; and major bleeding 13.2% during a median follow-up of 632 days (interquartile range: 187 to 1,126 days). MACE occurred in 35.4% and 40.0% of patients with total LVT regression and those with persistent LVT (p = 0.203). A reduced risk of mortality was observed among patients with total LVT regression (HR: 0.48; 95% CI: 0.23 to 0.98; p = 0.039), whereas an increased major bleeding risk was observed among patients with persistent LVT (9.1% vs. 12%; HR 0.34; 95% CI: 0.14 to 0.82; p = 0.011). A left ventricular ejection fraction ≥35% (HR: 0.46; 95% CI: 0.23 to 0.93; p = 0.029) and anticoagulation therapy >3 months (HR: 0.42; 95% CI: 0.20 to 0.88; p = 0.021) were independently associated with less MACE.Conclusions: The presence of LVT was associated with a very high risk of MACE and mortality. Total LVT regression, obtained with different anticoagulant regimens, was associated with reduced mortality. [ABSTRACT FROM AUTHOR]

Background: Serum cholesterol efflux capacity, a biomarker that integrates contributors and modulators of the initial step of the reverse cholesterol transport, has been associated with atherosclerosis independently of high-density lipoprotein (HDL) cholesterol level.Objectives: The authors evaluated the prognostic impact of serum cholesterol efflux capacity on mortality in a large cohort of patients hospitalized for an acute myocardial infarction (MI).Methods: Serum cholesterol efflux capacity, cholesteryl ester transfer protein (CETP) activity, total cholesterol, low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride levels were measured in 1,609 consecutive patients admitted with an acute MI. The primary endpoint was all-cause mortality evaluated at 6 years with a median follow-up of 1.9 years (interquartile range: 1.5 to 4.2 years). An analysis by quartile of serum cholesterol efflux capacity was also performed.Results: In a fully adjusted model that included age, sex, traditional cardiovascular risk factors including lipid levels, and prognostic factors of MI, serum cholesterol efflux capacity was a strong predictor of survival (adjusted hazard ratio for mortality per 1-SD increase in serum cholesterol efflux capacity, 0.79; 95% confidence interval: 0.66 to 0.95; p = 0.0132). Patients displaying an elevated serum cholesterol efflux capacity had a marked lower rate of mortality at 6 years (adjusted hazard ratio: 0.54 [0.32 to 0.89]; p = 0.0165) as compared with patients with reduced serum cholesterol efflux capacity.Conclusions: Serum cholesterol efflux capacity, an integrative marker of reverse cholesterol transport pathway and efficacy, was inversely associated with all-cause mortality in MI patients independently of HDL cholesterol level and other risk factors. [ABSTRACT FROM AUTHOR]