Recent Acute Coronary Syndrome Research Articles

Family History of Premature Coronary Heart Disease and Risk Factor Control in Patients With a Recent Acute Coronary Syndrome

Family History of Premature Coronary Heart Disease and Risk Factor Control in Patients With a Recent Acute Coronary Syndrome

Serum levels of soluble receptor activator for nuclear factor kB ligand play a crucial role in the association of osteoprotegerin with coronary artery disease.

Osteoprotegerin (OPG) is a soluble decoy receptor for receptor activator of nuclear factor kB ligand (RANKL), and is implicated in the pathogenesis of atherosclerosis. The aim of the present study was to examine the hypothesis that serum OPG concentrations are increased in patients with stable coronary artery disease (CAD) at different serum levels of soluble RANKL (sRANKL). The study used a case-control design in which consecutively hospitalized individuals were recruited. Fasting blood samples were taken upon admission for serum testing. Participants with previously diagnosed CAD that was asymptomatic or had controlled symptoms constituted the stable CAD group, whereas patients with negative coronary computed tomography angiography results constituted the control non-CAD group. Exclusion criteria included recent acute coronary syndrome, severe heart failure, CAD-complicating autoimmune, blood or thyroid diseases, cancer, elevated temperature with or without infection, severe liver or kidney dysfunction, abnormal calcium metabolism, recent surgery and trauma history. A total of 118 individuals were included in the study. Smoothed plots generated using the recursive method and multivariate models showed that the incidence of stable CAD increased with serum OPG level up to the turning point of 18 pg/ml. This trend was observed at both high [odds ratio (OR), 1.61; 95% confidence interval (CI), 1.04-2.50; P=0.032) and low sRANKL concentrations (OR, 1.52; 95% CI, 1.06-2.17; P=0.022) after adjustment for cardiovascular risk factors. In conclusion, serum OPG levels ≤18 pg/ml are positively associated with stable CAD, regardless of sRANKL levels. In addition, at the same serum OPG level, higher sRANKL levels are associated with a greater incidence of stable CAD compared with lower sRANKL levels. This study identified the relationship between OPG, sRANKL, and stable CAD, and established the reference range for future clinical use.

Risk-stratified analysis of long-term clinical outcomes and cumulative costs in Finnish patients with recent acute coronary syndrome or coronary revascularization: a 5-year real-world study using electronic health records.

Risk assessment is essential in the prevention of cardiovascular disease. In patients with recent acute coronary syndrome (ACS) or coronary revascularization, risk prediction tools, like the European Society of Cardiology guideline recommended SMART-REACH risk score, are increasingly used to predict the risk of recurrent cardiovascular events enabling risk-based personalized prevention. However, little is known about the association between risk stratification and the social and healthcare costs at a population level. This study evaluated the associations between baseline SMART-REACH risk scores, long-term recurrent clinical events, cumulative costs, and post-index event LDL-C goal attainment in patients with recent ACS and/or revascularization. This retrospective study used electronic health records and was conducted in the North Karelia region of Finland. The study cohort included all patients aged 45-85 admitted to a hospital for ACS or who underwent percutaneous coronary intervention or coronary artery bypass surgery between 1 January 2017 and 31 December 2021. Patients were divided into quintiles based on their baseline SMART-REACH risk scores to examine the associations between predicted 5-year scores and selected clinical and economic outcomes. In addition, simple age-based stratification was conducted as a sensitivity analysis. The observed 5-year cumulative incidence of recurrent events ranged from 20% in the lowest to 41% in the highest risk quintile, whereas the corresponding predicted risks ranged from 13% to 51%, and cumulative 5-year mean total costs per patient ranged from 15 827 to 46 182€, respectively. Both monitoring and attainment of low LDL-C values were suboptimal. The use of the SMART-REACH quintiles as a population-level risk stratification tool successfully stratified patients into subgroups with different cumulative numbers of recurrent events and cumulative total costs. However, more research is needed to define clinically and economically optimal threshold values for a population-level stratification.

Influence of matrix metalloproteinase 9 variant rs17576 on ischemic stroke risk and severity in acute coronary syndrome

BackgroundIschemic injury is a common mechanism in both ischemic stroke (IS) and acute coronary syndrome (ACS). Matrix metalloproteinase 9 (MMP-9), an endopeptidase that degrades extracellular matrix, is important in the pathogenesis of IS. The purpose of this study is to evaluate the association between the SNP rs17576 in MMP-9 gene with (1) the risk and severity of acute ischemic stroke in Saudi Arab individuals with recent acute coronary syndrome, and (2) the risk of acute coronary syndrome in Saudi Arab individuals without ischemic stroke. MethodsA case control study of 200 IS patients, 520 ACS patients (without IS), and 500 aged-matched healthy controls were genotyped to detect the MMP-9 polymorphism rs17156. ResultsOur study demonstrated a non-significant difference in the genotype and allele frequencies of the MMP9 rs17576 polymorphism between the patients with IS and patients with ACS without IS (P = 0.31 for the GA genotype, 0.25 for the AA genotype and P = 0.20 for the A allele). AA genotype was found to be statistically significant between IS and control groups; [OR=1.84, 95 % CI (1.08-3.14), p =0.015]. A allele showed a significant difference between the two groups [OR=1.28, 95 % CI (1.00-1.64), p =0.028]. By comparing ACS without IS and controls, AA genotype was significant [OR=1.46, 95 % CI (1.01–2.12), p =0.029]. Stratification by NIHSS score revealed higher mortality and early neurologic deterioration in IS patients with NIHSS score ≥ 16 (p < 0.001, 0.044 respectively). ConclusionWe deduced the lack of association either with allele or genotype frequencies (p>0.05) between the IS cases and the cases of ACS without IS. In contrast there was a significant association of mutant genotype AA between either the IS group or ACS (without IS) group, and the control group. In addition, different rs17576 genotypes were not associated with raised mortality or a tendency to develop early neurologic deterioration.

WEARABLE CARDIOVERTER–DEFIBRILLATORS IN CLINICAL PRACTICE IMPLEMENTATION OF THE ANMCO POSITION PAPER FOR APPROPRIATE USE OF THE WEARABLE CARDIOVERTER DEFIBRILLATOR

Abstract Introduction Wearable cardioverter–defibrillators (WCD) have emerged as a valuable tool in the management of patients at risk for life–threatening arrhythmias. These devices offer a non–invasive and temporary solution, providing continuous monitoring and the potential for prompt defibrillation when needed. In this study, we explore the indications for WCD and evaluate arrhythmic events through comprehensive monitoring. Methods From November 2022 to December 2023, we conducted an outpatient follow–up of 18 patients receiving WCD. Regular check–ups and comprehensive echocardiography were performed to optimize therapy based on specific indications for each patient. Results The average age of the patients was 59.3±17.4 years, with 79% being male. Among the cohort, 58% had hypertension, and a similar percentage comprised smokers and individuals with dyslipidemia, while 32% were diabetic. The indications for receiving WCD were: de novo diagnosis of dilated cardiomyopathy with reduced ejection fraction in 9 (50%) patients, recent acute coronary syndrome and ejection fraction &amp;lt; 35% in 5 (28%), cardiac electronic device infections in 3 (17%) patients and myocarditis with electrical instability in 1 (5%) patient. Patients were in optimal medical therapy (OMT) tailored to their specific comorbidities, with 84% on renin–angiotensin–aldosterone system inhibitors, 95% on beta–blockers, 53% on mineralocorticoid receptor antagonists, 53% on sodium–glucose cotransporter–2 inhibitors, and 37% on antiarrhythmics. The average follow–up was 64±45 days according to specific etiology, with a daily wearing time of 22.9±1.1 hours. No device interventions were recorded. At the end of the follow–up period, 6 (33%) patients still required implantable cardioverter–defibrillator (ICD). Among these, 4 patients (22%) underwent to ICD implantation, 3 for secondary prevention, and 1 for primary prevention, while notably, 2 (11%) patients, declined the procedure. Conclusions The use of wearable cardioverter–defibrillators in the outpatient setting for patients at risk of life–threatening arrhythmias allowed to optimize therapy and restrict the indications for ICD, in our cohort up to 67%, with a good safety profile due to the low incidence of device interventions.

Assessment of medical risks in airline passengers with recent acute and chronic coronary syndromes

This review provides a summary of data on the health status of adults with cardiovascular disease during air travel. We describe mental and physical stressors affecting the cardiovascular system and hypobaric hypoxia in the commercial aircraft cabin. Valid algorithms for preliminary assessment of the condition of patients with recent acute and chronic coronary syndromes are proposed.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: a report from the ODYSSEY OUTCOMES study

BackgroundThe ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). ObjectiveWe assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. MethodsThis prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. ResultsWomen were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. ConclusionsAlirocumab improves cardiovascular outcomes after ACS irrespective of sex. Reduction of total cardiovascular events was greater at higher baseline lipoprotein(a).

Myocardial Perfusion Imaging and C-Reactive Protein in Myocardial Ischemia: A Retrospective Single-Center Study.

Inflammation is an important mechanism in atherosclerosis and plaque formation. C-reactive protein (CRP) is a common inflammatory biomarker associated with the risk of coronary heart disease. We investigated the relationship of CRP with findings from myocardial perfusion imaging (MPI). In this retrospective study, 102 consecutive patients (mean age 71 years, 68% males) who underwent MPI (for diagnostic reasons or quantification of myocardial ischemia) and CRP determination (upper limit: 6 mg/L) within 1 month from MPI were included. The patients had no infection or recent acute coronary syndrome. The median CRP level was 4 mg/L (2, 10) among the study population. Patients with raised CRP had higher summed stress score (SSS) (p = 0.006) and summed rest score (SRS) (p = 0.001) and higher risk for SSS > 3 (OR 9.25, 95% CI 2.03-42.13, p = 0.001) compared to those with low CRP. The association of SSS and SRS with CRP levels was more evident in patients over 70 years (p = 0.027 and p = 0.005, respectively). No significant difference in summed difference score was shown. The two groups had no difference in other risk factors (p > 0.05 for all comparisons). a high level of CRP was associated with the presence and extent of stress-induced myocardial ischemia in MPI.

In-Hospital influenza vaccination to prevent cardiorespiratory events in the first 45 days after acute coronary syndrome: A prespecified analysis of the VIP-ACS trial

BackgroundInfluenza vaccination prevents major cardiovascular events in individuals presenting a recent acute coronary syndrome (ACS), however the early effect of an in-hospital double-dose vaccination strategy remains uncertain. MethodsThe VIP-ACS was a randomized, pragmatic, multicenter, open-label trial with a blinded-adjudication endpoint. Patients with ACS ≤ 7 days of hospitalization were randomized to an in-hospital double-dose quadrivalent inactivated influenza vaccine (double-dose) or a standard-dose influenza vaccine at 30 days post-randomization. The primary endpoint was a hierarchical composite of death, myocardial infarction, stroke, hospitalization for unstable angina, hospitalization for heart failure, urgent coronary revascularization, and hospitalization for respiratory infections, analyzed with the win ratio (WR) method in short-term follow-up (45-days after randomization). ResultsThe trial enrolled 1,801 patients (≥18 years old). Median participant age was 57 years, 70 % were male. There were no significant differences between groups on the primary hierarchical endpoint: there were 5.7 % wins in the double-dose in-hospital group and 5.5 % wins in the standard-dose delayed vaccination group (WR: 1.03; 95 % CI: 0.70–––1.53; P = 0.85). In a sensitivity analysis including COVID-19 infection in the hospitalizations for respiratory infections endpoint, overall results were maintained (WR: 1.03; 95 % CI 0.71–––1.51; P = 0.87). Results were consistent for major cardiovascular events only (WR: 0.82; 95 % CI: 0.48–––1.39; P = 0.46). No serious adverse events were observed. ConclusionIn patients with recent ACS, in-hospital double-dose influenza vaccination did not significantly reduce cardiorespiratory events at 45 days compared with standard-dose vaccination at 30 days post-randomization.

Two of a kind: mass and molar immunoassay-based lipoprotein (a) concentrations are similarly prognostic for MACE risk and predictive of alirocumab benefit in ODYSSEY OUTCOMES

Abstract Background Lipoprotein (a) (Lp(a)) is a risk factor for incident and recurrent ischemic cardiovascular (CV) events and may modify the benefit of PCSK9 inhibitors (PCSK9i). While Lp(a) concentration can be measured in either mass or molar units, to date there has been no direct, large-scale comparison of the relationships of mass vs. molar Lp(a) with CV risk and response to treatment. Purpose Using samples from ODYSSEY OUTCOMES where 18,924 patients with recent acute coronary syndrome were randomized 1:1 to the PCSK9i alirocumab (ALI) or placebo (PBO), baseline mass vs. molar Lp(a) were compared in terms of prognosis for first major adverse CV event (MACE, consisting of coronary heart disease death, nonfatal myocardial infarction, ischemic stroke, or hospitalization for unstable angina) in the placebo group and associations with ALI risk reduction. Methods Lp(a) mass and molar tests were the Siemens N latex immunonephelometric test and the Roche TinaQuant immunoturbidimetric assay, respectively. Both tests use polyclonal anti-apo(a) antibodies but are designed to be relatively apo(a)-size independent within allowable measurement uncertainty. Absolute risk of MACE at 4 years in the PBO group and treatment risk ratios (RR) by continuous Lp(a) concentrations were estimated by natural cubic splines from Poisson regression models with log follow-up time as an offset and adjustment for baseline LDL-C. For comparative modeling purposes Lp(a) values were transformed into percentiles; due to ties at the lower limits of quantification, minimum percentiles were 8th and 6th for mass and molar, respectively. All analyses were intention-to-treat. Results Baseline mass and molar Lp(a) concentrations, available in 11943 patients, were correlated (r=0.94). ALI MACE reduction in evaluable patients (1324 events; RR [95% CI] = 0.83 [0.74, 0.92]) was similar to the total population (1955 events; RR [95% CI] = 0.85 [0.78, 0.93]). Relationships with risk of MACE in the PBO group were nearly identical for mass (spline p=0.0001) and molar (spline p=0.0002) concentrations (Figure 1). Of note, the confidence boundaries around the splines were nearly superimposable, indicating similar precision of the estimated Lp(a)-associated risk with both measurement techniques. Risk reductions with ALI were similarly related to mass (spline p&amp;lt;0.0001) and molar (spline p&amp;lt;0.0001) concentrations (Figure 2). Conclusion Baseline mass and molar Lp(a) concentrations were similarly prognostic for MACE risk in the PBO group after adjustment for LDL-C. Mass and molar Lp(a) also similarly modified the ALI treatment effect on MACE, with trends towards less treatment benefit at lower concentrations. These results suggest that, at the treatment group level, the prognostic and predictive value of immunoassay-based Lp(a) tests for ischemic CV events in patients with recent acute coronary syndrome is not meaningfully different for the mass or molar concentration essays that were evaluated.Figure 1Figure 2

The role of seasonal influenza immunisation in cardiovascular care: a survey of cardiologists

Abstract Background Seasonal influenza immunisation reduces cardiovascular events by 30% in those with atherosclerotic cardiovascular disease (ASCVD) and up to 50% in those with recent acute coronary syndrome. However, uptake in high-risk patients remains poor. Clinician recommendation has been shown to increase adoption of influenza immunisation in the general population; thus, cardiologists are well-placed to promote uptake in patients with cardiovascular disease. Purpose To describe the attitudes and behaviours of Australian cardiologists regarding seasonal influenza immunisation. Methods We used an exploratory sequential mixed methods design. Semi-structured interviews of 10 cardiologists were performed to identify themes for quantitative evaluation in an online survey. Multiple choice and Likert scale questions explored (a) attitudes and behaviours regarding influenza immunisation, (b) engagement with colleagues and professional bodies and (c) preventative care in cardiology. The survey was administered to 63 cardiologists between November 2020 and January 2021 and respondents received an honorarium for their time. Results The majority of respondents were general cardiologists (50/63) – compared with subspecialist cardiologists, and had spent an average of 21 years in practice. Less than half of the cardiologists surveyed asked patients about their vaccination status always or most of the time (46%, 29/63). Only one quarter (25.4%, 16/63) of cardiologists recommended influenza immunisation to all of their patients while higher proportions recommended it among patients with ASCVD (49.2%, 31/63), heart failure (69.8%, 44/63) and those over the age of 65 years (68.3%, 44/63). Just over half of the cardiologists (57.1%, 36/63) agreed that influenza immunisation was important/very important for prevention of cardiac events, however this was of lower priority compared with other components of preventive care including smoking cessation (100% agreed important, 63/63), anti-hypertensives (96.8%, 61/63), statins (94.3%, 60/63), exercise (80.9%, 51/63), anticoagulants (74.6%, 47/63), SGLT2 inhibitors (69.8%, 44/63) and diet (68.2%, 43/63). Three quarters of cardiologists (76.2%, 48/63) believed that the clinician predominantly responsible for ensuring that patients received the immunisation was the general practitioner, with only a minority (12.7%, 8/63) reporting that it was the role of the cardiologist. Conclusions Despite a relative risk reduction exceeding that of statins and antihypertensives for patients with CVD, influenza immunisation is not prioritized or recommended by many cardiologists. Efforts at increasing awareness and advocacy among cardiologists may assist in broadening uptake among high-risk patients with cardiovascular disease.

Abstract 13567: Comparison of Change in Lipoprotein(a) Mass and Molar Concentrations by Alirocumab and Risk of Subsequent Cardiovascular Events in ODYSSEY OUTCOMES

Background: Baseline (BL) lipoprotein(a) (Lp(a)) concentration is similarly related to cardiovascular (CV) risk when measured in either mass or molar units by immunoassay (IA). Because of Lp(a) isoform variation in mass, differences may exist between Lp(a) measurement methods in terms of relating change to risk reduction. We determined whether the reduction in major adverse cardiovascular events (MACE) by PCSK9 inhibitor alirocumab (ALI) had a similar relationship to the reduction in Lp(a) concentration as measured by 3 different methods. Methods: Lp(a) was measured by IA-mass (Siemens), IA-molar (Roche), and mass spectrometry (MS)-molar assays at BL and month 4 (M4) in a subgroup of patients in the ODYSSEY OUTCOMES trial which compared PCSK9 inhibitor ALI with placebo in patients with recent acute coronary syndrome. Changes in Lp(a) from BL to M4 were related to subsequent risk of MACE (coronary heart disease (CHD) death, nonfatal myocardial infarction (NFMI), fatal + nonfatal ischemic stroke, or unstable angina hospitalization) in the ALI group. Proportional hazards models were adjusted for BL Lp(a), BL LDL-C and its change from BL to M4, and other patient characteristics. Hazard ratios (HR) were calculated for the median change of each Lp(a) assay. All analyses were by intention-to-treat. Results: Among 5500 patients randomized to ALI with available data from all 3 Lp(a) assays, 443 experienced a subsequent MACE. Changes in Lp(a) IA-mass and MS-molar concentration were significantly related to reduced MACE risk, while change in IA-molar concentration was marginally significant; associations were more evident with CHD death + NFMI ( Figure ). MACE HRs for median change were similar across tests. Conclusion: With caveats of a modest number of MACE for analysis, moderately elevated Lp(a) levels, and intra-patient variability in serial values, 3 Lp(a) assay methods appeared similarly predictive of ALI MACE reduction.

Abstract 14234: Fast Track Use of PCSK9i in Acute Coronary Syndromes in Real World Practice. Insights From the AT-TARGET-IT Registry

Introduction: In patients with recent acute coronary syndrome (ACS), PCSK9 inhibitors (PCSK9i), alirocumab and evolocumab, intensively decrease LDL-C and determine reduction of ischemic events. Yet, scant data are available on the initiation of PCSK9i in ACS patients in real-world setting. Aim: AT-TARGET-IT is an Italian multicenter prospective phase 4 registry involving 23 centers, designed to assess efficacy, safety and adherence of PCSK9i, as well as clinician’s behavior on lipid lowering therapies (LLT) in patients at very high CV risk. Aim of the current analysis is to report efficacy and safety in patients suffering ACS who received early prescription of PCSK9i during hospital stay, according to national reimbursement rules. Methods: From March 2020 through May 2023, we enrolled patients receiving PCSK9i as part of their optimal medical therapy. Clinical, laboratory and demographic characteristics and concomitant therapies were recorded at the time of first prescription and in subsequent follow-up. Results: We report 405 patients (22% female, age 61 years, 60% chronic coronary syndromes). Median LDL-C was 142 mg/dL at hospital admission, reached 45 mg/dL at first control (time 37 days, 67% reduction, 97 mg/dl absolute reduction) and remained unchanged at latest lipid control (time 11 months, 66% reduction, 94 mg/dl absolute reduction). Of 405 patients enrolled, 252 patients (62%) were receiving LLT at time of hospital admission, of them 91 (36%) were on ezetimibe, 48 (19%) on statin and 113 (45%) were on a statin and ezetimibe combination. LDL-C target according to the ESC guidelines was reached in 272 patients (67%), with differences based on LLT (Figure 1-A). Also LDL-C percentage reduction was influenced by background LLT (Figure 1-B). No serious adverse reactions were reported. Conclusions: Early PCSK9i administration effectively reduces LDL-C in ACS patients in the real-world setting. However, concomitant LLT is needed to optimize early LDL.values.

Pathophysiological Sex Differences in Heart Failure Progression After Acute Coronary Syndrome: Insights From the EXAMINE Trial

BackgroundTherapies can reduce the risk of heart failure (HF) development and progression in type 2 diabetes; nevertheless, the risk of these outcomes is greater in females than in males. Methods and ResultsTo investigate sex differences in HF development and progression, we compared baseline circulating proteins (Olink Cardiovascular II panel) in males and females with type 2 diabetes and recent acute coronary syndrome for the outcome of HF hospitalization. Data were from the placebo-controlled Examination of Cardiovascular Outcomes with Alogliptin vs Standard of Care (EXAMINE) trial. Pathophysiological sex-differences were interpreted with network and pathway over-representation analyses. The EXAMINE trial enrolled 5380 participants (32.1% females) with biomarker data available for 95.4% of individuals. Analyses revealed 43 biomarkers were differentially expressed in HF hospitalization, of which 18 were sex specific. Among these 43 biomarkers, interleukin-6 was identified as a central node for the pathogenesis of HF hospitalization in both females and in males. Additional pathway over-representation analyses demonstrated that biomarkers associated with inflammatory pathways related to endothelial dysfunction and cardiac fibrosis were more up-regulated in females than males with HF hospitalization. Differential expression of 3 biomarkers (pentraxin-related protein 3, hydroxyacid oxidase 1, and carbonic anhydrase 5A) was independently associated with an increased risk of HF hospitalization in females but not in males (interaction P < .05). ConclusionsIn males and females with type 2 diabetes and acute coronary syndrome, interleukin-6 seems to be central in the pathogenesis of HF. Females exhibit higher levels of circulating proteins related to immunological pathways, reflecting sex-specific differences underlying HF development and progression.

Relating Lipoprotein(a) Concentrations to Cardiovascular Event Risk After Acute Coronary Syndrome: A Comparison of 3 Tests.

Lipoprotein(a) is a risk factor for cardiovascular events and modifies the benefit of PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors. Lipoprotein(a) concentration can be measured with immunoassays reporting mass or molar concentration or a reference measurement system using mass spectrometry. Whether the relationships between lipoprotein(a) concentrations and cardiovascular events in a high-risk cohort differ across lipoprotein(a) methods is unknown. We compared the prognostic and predictive value of these types of lipoprotein(a) tests for major adverse cardiovascular events (MACE). The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the PCSK9 inhibitor alirocumab with placebo in patients with recent acute coronary syndrome. We compared risk of a MACE in the placebo group and MACE risk reduction with alirocumab according to baseline lipoprotein(a) concentration measured by Siemens N-latex nephelometric immunoassay (IA-mass; mg/dL), Roche Tina-Quant turbidimetric immunoassay (IA-molar; nmol/L), and a noncommercial mass spectrometry-based test (MS; nmol/L). Lipoprotein(a) values were transformed into percentiles for comparative modeling. Natural cubic splines estimated continuous relationships between baseline lipoprotein(a) and outcomes in each treatment group. Event rates were also determined across baseline lipoprotein(a) quartiles defined by each assay. Among 11 970 trial participants with results from all 3 tests, baseline median (Q1, Q3) lipoprotein(a) concentrations were 21.8 (6.9, 60.0) mg/dL, 45.0 (13.2, 153.8) nmol/L, and 42.2 (14.3, 143.1) nmol/L for IA-mass, IA-molar, and MS, respectively. The strongest correlation was between IA-molar and MS (r=0.990), with nominally weaker correlations between IA-mass and MS (r=0.967) and IA-mass and IA-molar (r=0.972). Relationships of lipoprotein(a) with MACE risk in the placebo group were nearly identical with each test, with estimated cumulative incidences differing by ≤0.4% across lipoprotein(a) percentiles, and all were incrementally prognostic after accounting for low-density lipoprotein cholesterol levels (all spline P≤0.0003). Predicted alirocumab treatment effects were also nearly identical for each of the 3 tests, with estimated treatment hazard ratios differing by ≤0.07 between tests across percentiles and nominally less relative risk reduction by alirocumab at lower percentiles for all 3 tests. Absolute risk reduction with alirocumab increased with increasing lipoprotein(a) measured by each test, with significant linear trends across quartiles. In patients with recent acute coronary syndrome, 3 lipoprotein(a) tests were similarly prognostic for MACE in the placebo group and predictive of MACE reductions with alirocumab at the cohort level. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01663402.

Mortality Prediction in Patients With or Without Heart Failure Using a Machine Learning Model

BackgroundMost risk prediction models are confined to specific medical conditions, thus limiting their application to general medical populations. ObjectivesThe MARKER-HF (Machine learning Assessment of RisK and EaRly mortality in Heart Failure) risk model was developed in heart failure (HF) patients. We assessed the ability of MARKER-HF to predict 1-year mortality in a large community-based hospital registry database including patients with and without HF. MethodsThis study included 41,749 consecutive patients who underwent echocardiography in a tertiary referral hospital (4,640 patients with and 37,109 without HF). Patients without HF were further subdivided into those with (n = 22,946) and without cardiovascular disease (n = 14,163) and also into cohorts based on recent acute coronary syndrome or history of atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, hypertension, or malignancy. ResultsThe median age of the 41,749 patients was 65 years, and 56.2% were male. The receiver operated area under the curves for MARKER-HF prediction of 1-year mortality of patients with HF was 0.729 (95% CI: 0.706-0.752) and for patients without HF was 0.770 (95% CI: 0.760-0.780). MARKER-HF prediction of mortality was consistent across subgroups with and without cardiovascular disease and in patients diagnosed with acute coronary syndrome, atrial fibrillation, chronic obstructive pulmonary disease, chronic kidney disease, diabetes mellitus, or hypertension. Patients with malignancy demonstrated higher mortality at a given MARKER-HF score than did patients in the other groups. ConclusionsMARKER-HF predicts mortality for patients with HF as well as for patients suffering from a variety of diseases.

Empagliflozin improves insulin sensitivity in patients with recent acute coronary syndrome and newly detected dysglycaemia

BackgroundEmpagliflozin reduces the risk of cardiovascular disease (CVD) in patients with type 2 diabetes (T2DM) and high cardiovascular risk via mechanisms which have not been fully explained. The mechanisms of such benefit have not been fully understood, and whether empagliflozin can be safely administered as first-line treatment in patients with CVD at the initial stages of glycaemic perturbations remains to be established. We investigated the effects of empagliflozin on insulin resistance, insulin sensitivity and β-cell function indexes in patients with a recent acute coronary event and newly detected dysglycaemia, i.e., impaired glucose tolerance (IGT) or T2DM.MethodsForty-two patients (mean age 67.5 years, 19% females) with a recent myocardial infarction (n = 36) or unstable angina (n = 6) and newly detected dysglycaemia were randomized to either empagliflozin 25 mg daily (n = 20) or placebo (n = 22). Patients were investigated with stress-perfusion cardiac magnetic resonance imaging before randomization, 7 months after the start of study drug and 3 months following its cessation. Indexes of insulin resistance, sensitivity and β-cell function were calculated based on glucose and insulin values from 2-hour oral glucose tolerance tests (OGTT) and fasting C-peptide. The differences in glucose, insulin, C-peptide, mannose levels and indexes between the two groups were computed by repeated measures ANOVA including an interaction term between the treatment allocation and the time of visit.ResultsAfter 7 months, empagliflozin significantly decreased glucose and insulin values during the OGTT, whereas C-peptide, mannose and HbA1c did not differ. Empagliflozin significantly improved insulin sensitivity indexes but did not impact insulin resistance and β-cell function. After cessation of the drug, all indexes returned to initial levels. Insulin sensitivity indexes were inversely correlated with left ventricular mass at baseline.ConclusionsEmpagliflozin improved insulin sensitivity indexes in patients with a recent coronary event and drug naïve dysglycaemia. These findings support the safe use of empagliflozin as first-line glucose-lowering treatment in patients at very high cardiovascular risk with newly diagnosed dysglycaemia.Trial registration numberEudraCT number 2015-004571-73.

Physical activity and sedentary behaviour changes during and after cardiac rehabilitation: Can patients be clustered?

Objective: To identify clusters of patients according to changes in their physical behaviour during and after cardiac rehabilitation, and to predict cluster membership.Methods: The study included 533 patients (mean age 57.9 years; 18.2% females) with a recent acute coronary syndrome who participated in a 12-week multi-disciplinary cardiac rehabilitation programme, within a cohort study design. Physical behaviour (light physical activity, moderate-to vigorous physical activity, step count, and sedentary behaviour) was measured using accelerometry at 4 timepoints. To identify clusters of patients according to changes in physical behaviour during and after cardiac rehabilitation, latent class trajectory modelling was applied. Baseline factors to predict cluster membership were assessed using multinomial logistic regression.Results: During and after cardiac rehabilitation, 3 separate clusters were identified for all 4 physical behaviour outcomes: patients with steady levels (comprising 68–83% of the patients), and improving (6–21%) or deteriorating (4–23%) levels. Main predictor for membership to a specific cluster was baseline physical behaviour. Patients with higher starting physical behaviour were more likely to be a member of clusters with deteriorating levels.Conclusion: Separate clusters of physical behaviour changes during and after cardiac rehabilitation could be identified. Clusters were mainly distinguished by baseline physical behaviour level. LAY ABSTRACTPhysical behaviour is a construct including both physical activity and sedentary behaviour. Healthy levels of physical behaviour are important for cardiac patients. Cardiac rehabilitation programs are designed to promote a heart-healthy lifestyle for this group. Nevertheless, not all patients perform sufficient physical activity after cardiac rehabilitation. It is important to identify patients at risk for disappointing physical behaviour outcomes at an early stage to provide additional care. Outcomes of the current study show that cardiac patients can be clustered according to their change in physical behavior during and after cardiac rehabilitation. The majority showed steady levels and no improvements, but we could also identify groups of patients with improving and deteriorating levels. Patients with higher starting physical activity levels or low sedentary behaviour levels were more likely to be a member of clusters with deteriorating levels. These patients could benefit of additional interventions.

Effect of alirocumab on cataracts in patients with acute coronary syndromes

BackgroundSome data suggest that low levels of low-density lipoprotein cholesterol (LDL-C) are associated with risk of cataracts. Proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors reduce LDL-C below levels achieved with statins alone. We determined whether the incidence of cataracts was influenced by treatment with the PCSK9 inhibitor alirocumab versus placebo, and whether that incidence was affected by achieved LDL-C levels.MethodsThe ODYSSEY OUTCOMES trial (NCT01663402) compared alirocumab with placebo in 18,924 patients with recent acute coronary syndrome receiving high-intensity or maximum-tolerated statin. Incident cataracts were pre-specified events of interest. In multivariable analysis using propensity score-matching on characteristics including cataract risk factors, incident cataracts were compared in the alirocumab and placebo groups according to LDL-C levels achieved with alirocumab.ResultsOver median follow-up of 2.8 years (interquartile range 2.3 − 3.4), the incidence of cataracts was similar with alirocumab (127/9462 [1.3%]) versus placebo (134/9462 [1.4%]); hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.74 − 1.20). In patients treated with alirocumab with ≥ 2 LDL-C values < 25 mg/dL (0.65 mmol/L), the incidence of cataracts was 71/4305 (1.6%), versus 60/4305 (1.4%) in propensity score-matched patients from the placebo group (HR 1.10, CI 95% 0.78 − 1.55). In patients treated with alirocumab with ≥ 2 LDL-C values < 15 mg/dL (0.39 mmol/L), the incidence of cataracts was 13/782 (1.7%), versus 36/2346 (1.5%) in matched patients from the placebo group (HR 1.03, CI 95% 0.54 − 1.94).ConclusionTreatment with alirocumab versus placebo, added to statin, did not influence the incidence of cataracts, even when achieved LDL-C levels on alirocumab were very low. Longer follow-up studies might be necessary to exclude the long-term effects on the incidence or progression of cataracts.Trial registrationClinicalTrials.gov Identifier: NCT01663402.

Machine learning models in predicting health care costs in patients with a recent acute coronary syndrome: A prospective pilot study

Health care budgets are limited, requiring the optimal use of resources. Machine learning (ML) methods may have an enormous potential for effective use of health care resources. We assessed the applicability of selected ML tools to evaluate the contribution of known risk markers for prognosis of coronary artery disease to predict health care costs for all reasons in patients with a recent acute coronary syndrome (n = 65, aged 65 ± 9 years) for 1-year follow-up. Risk markers were assessed at baseline, and health care costs were collected from electronic health registries. The Cross-decomposition algorithms were used to rank the considered risk markers based on their impacts on variances. Then regression analysis was performed to predict costs by entering the first top-ranking risk marker and adding the next-best markers, one by one, to build up altogether 13 predictive models. The average annual health care costs were €2601 ± €5378 per patient. The Depression Scale showed the highest predictive value (r = 0.395), accounting for 16% of the costs (P = .001). When the next 2 ranked markers (LDL cholesterol, r = 0.230; and left ventricular ejection fraction, r = -0.227, respectively) were added to the model, the predictive value was 24% for the costs (P = .001). Higher depression score is the primary variable forecasting health care costs in 1-year follow-up among acute coronary syndrome patients. The ML tools may help decision-making when planning optimal utilization of treatment strategies.