Myocardial Infarction Death Research Articles

Effectiveness and Safety of the ESC-TROP (European Society of Cardiology 0h/1h Troponin Rule-Out Protocol) Trial.

European guidelines recommend the use of a 0h/1h hs-cTn (high-sensitivity cardiac troponin) protocol in patients with acute chest pain. We aimed to determine the performance of this protocol in routine care when supplemented with patient history and ECG and a recommendation to refrain from noninvasive testing in low-risk patients. This was a pre- and postimplementation study with concurrent controls. Patients with chest pain were enrolled at 5 Swedish emergency departments (EDs) during a 10-month period in both 2017 and 2018. All hospitals used a 0h/3h hs-cTnT protocol in 2017 and 3 EDs implemented a 0h/1h hs-cTnT protocol during 10 months in 2018. The 2 coprimary outcomes were the incidence of acute myocardial infarction and all-cause death within 30 days and ED length of stay. The study included 26 040 consecutive patients. In the intervention hospitals, 21 (0.40%) of the discharged patients had an acute myocardial infarction/death event during the control period (0h/3h testing) and 22 (0.45%) in the intervention period (0h/1h testing), which met the criteria for noninferiority. There was no significant difference in ED length of stay (ratio 0.99, P=0.48) or ED discharge rate between the periods in the intervention versus the control hospitals. A total of 3142 patients met low-risk 0h/1h hs-cTnT criteria and were discharged, of whom 2 had an acute myocardial infarction/death event. A 0h/1h hs-cTnT protocol incorporating patient history and ECG was as safe as using a 0h/3h protocol but did not reduce ED length of stay or increase the discharge rate. Refraining from noninvasive testing in patients identified as low risk was safe. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03421873.

Adverse cardiovascular outcomes due to potential drug-drug interactions in statin therapy: a population-based study

Abstract Background Statins have been proven to reduce morbidity and mortality in patients with known atherosclerotic cardiovascular disease (ASCVD) and in primary prevention. Given their unique role in ASCVD, concomitant use of statins and other medications are inevitable. Our clinicians’ duty is to identify clinically important drug-drug interactions (DDI) with statins and to minimize potential life-threatening adverse drug reactions. Purpose To understand the clinical relevance of statin related DDI, we aimed to analyse the prevalence and level of severity of potential statin DDI in a real-world territory-wide population-based study. Methods We retrospectively analysed 95278 patients (mean age 64.3±11.4, female 45.0%) prescribed simvastatin (N=56111, 59%), atorvastatin (N=33902, 36%), or rosuvastatin (N=5265, 5%) from 2013-2022 among 16 public hospitals. Covariates were balanced with 1:1 propensity score matching for patients with and without potential DDI, resulting in 35907 patients in each arm. A composite 4-point MACE (major adverse cardiovascular events) was used as the primary outcome, which included coronary revascularisation, stroke, myocardial infarction (MI), and cardiovascular-related death (CV death). Cox proportional-hazard model with competing risk regression was performed to estimate adjusted hazards ratio (aHR) with corresponding 95% confidence intervals (CI). Secondary analyses would be focusing on adverse drug reactions in these three different statin subgroups. Results At 1-year follow up, subjects with potential statin related DDI have higher propensities of deranged liver function (ALT>=3x ULN, 4.9% vs 3.4%; p<0.001), elevated creatine kinase (CK>=5x ULN, 0.9% vs 0.5%, p<0.001) and deranged renal function (creatinine level >=2X ULN, 0.3% vs 0.2%, p<0.001) than non-DDI group. At 5-year follow up, the statin DDI group had higher incidences of MI (2.9% vs 1.9%, p<0.01), stroke (4.0% vs 2.3%, p<0.001) and CV death (1.7 % vs 1.5%, p=0.038). Potential DDI had most significant effect seen on simvastatin compared to other statins. Simvastatin DDI cohort had strong association with subsequent coronary vascularization (aHR 1.41, 95% CI 1.21–1.64, p<0.005), MI (aHR 1.66, 95% CI 1.46–1.88, p<0.005), stroke (aHR 1.95, 95% CI 1.76–2.16, p<0.005), and CV-related death (aHR 1.18, 95% 1.00–1.38, p=0.05) as compared to control. Atorvastatin DDI cohort was associated with higher rates of MI (aHR 1.81, 95% CI 1.54–2.12, p<0.005) and stroke (aHR 1.64, 95% CI 0.39–1.94, p<0.005) than control. Rosuvastatin DDI cohort was weakly associated with higher rates of MI (aHR 1.75, 95% CI 1.02–3.01, p=0.04). Conclusion Potential statin related drug-drug interactions are prevalent and were associated with major adverse cardiovascular events. Our real-world data demonstrated that simvastatin related drug-drug interaction pose a significant threat to our patients with association with CV death, myocardial infarction, stroke and future coronary revascularization.4-point MACE

Angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers vs. calcium channel blockers for 12,478 young hypertensive patients under 40 in 10-year follow-up

Abstract Background It is uncertain whether angiotensin-converting enzyme inhibitors (ACEIs)/ angiotensin-receptor blockers (ARBs) is superior to calcium channel blockers (CCBs) in young hypertensive patients. Purpose To compare ACEIs/ARBs with CCBs in hypertensive patients <40 years for 10years. Methods We enrolled adults aged 20-39 with hypertension from 2007-2010 using the Korean national Insurance. Among 409,151 hypertensive patients, we made propensity matched analysis to compare the 2 drugs. Results 12,478 patients were enrolled, 6239 in ACEIs/ARBs and 6239 in CCBs group. Primary endpoint of a composite of myocardial infarction (MI), heart failure (HF), stroke, and total death was similar in 2 groups in young hypertensive patients in 10-year follow-up: 662 (ACEIs/ARBs) vs. 642/10000 (CCBs) with hazard ratio (HR) of 1.03 (reference, CCBs) (CI 0.90-1.18, P=0.657). In individual event of a MI, HF, stroke and total death, there was no difference in 2 groups: 99 vs 128/10000 persons (ACEIs/ARBs and CCBs respectively) with HR 0.77 (CI 0.56-1.08, P=0.13) in MI, 114 vs. 87/10000 (HR 1.32, P=0.123) in HF, 314 vs. 306 /10000 (HR 1.03, CI 0.64-1.20, P=0.795) in stroke and 184 vs. 167/10000 (HR 1.11, CI 0.85-1.44, P=0.454) in total death. Conclusions In young hypertensive patients, ACEIs/ARBs did not superior to CCBs in 10year clinical follow-up in large population.

Composition of non-HDL cholesterol and residual cardiovascular risk in secondary prevention

Abstract Background Non-high-density lipoprotein cholesterol (non-HDL-C) is associated with atherosclerotic cardiovascular disease (ASCVD) and is a recommended secondary prevention treatment target. However, the composition of non-HDL-C, that is, the relative contribution of remnant cholesterol (remnant-C) and low-density-lipoprotein cholesterol (LDL-C), is not considered for cardiovascular risk prediction. Purpose To examine ASCVD risk by composition of non-HDL-C. Methods Based on the Western Denmark Heart Registry, we established a cohort of patients with ischemic heart disease, including patients with acute coronary syndrome or stable angina pectoris, undergoing coronary angiography for evaluation of coronary artery disease between 2011 and 2020. A complete lipid panel within 1 year after coronary angiography on statin treatment was required. Patients with triglycerides >4.5 mmol/L were excluded. Exposures were remnant-C, LDL-C, non-HDL-C, and composition of non-HDL-C. The latter was defined as remnant-C of non-HDL-C, and LDL-C of non-HDL-C, in percentages. Cox regression analyses obtained adjusted hazard ratios (aHR) for myocardial infarction, ASCVD (myocardial infarction, ischemic stroke, and cardiovascular death), and all-cause death occurring from 1 year after coronary angiography to end of follow-up November 1, 2022. Results The secondary prevention cohort included 42,341 statin-treated patients (67.7% were men; median [IQR] age 66 [58-73] years). During median 4.1 years of follow-up, 3,846 patients developed ASCVD. Per 1 mmol/L increase in remnant-C, LDL-C, and non-HDL-C, the aHR for ASCVD was 1.41 (95% CI 1.28-1.55), 1.12 (95% CI 1.08-1.17), and 1.17 (95% CI 1.13-1.21), respectively (Figure 1). The relative contribution of remnant-C and LDL-C was median (IQR) 24.6% (18.5-33.1) and 75.4% (66.9-81.5) of non-HDL-C, respectively. When remnant-C constituted a larger percentage of non-HDL-C (and LDL-C a lower percentage), the aHR for ASCVD showed a linear increase in risk whereas the opposite trend was observed for LDL-C (Figure 2). Thus, per 10% increase in remnant-C of non-HDL-C, the aHR of ASCVD was 1.06 (95% CI 1.03-1.09) compared to 0.94 (95% CI 0.91-0.97) per 10% increase in LDL-C of non-HDL-C. Results were comparable for myocardial infarction and all-cause death, and by age, sex, and other clinically relevant subgroups. Conclusions The composition of non-HDL-C is strongly associated with ASCVD risk, with the risk escalating as remnant-C constitutes a larger percentage, and LDL-C a smaller percentage, of non-HDL-C. These findings challenge current guidelines and demonstrate the value of considering composition of non-HDL-C in clinical practice for more accurate risk assessment.Figure 1Figure 2

Lipid lowering therapy in patients aged 90 years or older with acute myocardial infarction:a multicenter cohort study

Abstract Background Lipid-lowing therapy significantly reduce adverse cardiovascular events in patients with acute myocardial infarction (AMI). However, evidence regarding the efficacy of lipid-lowing therapy in extremely elderly patients with AMI is limited. Purpose This study aims to evaluate major adverse cardiovascular events (MACCE) at 1 year in relation to taking lipid-lowing therapy (statins) among patients aged 90 years or older. Methods The data for this study were derived from a retrospective cohort comprising patients admitted to secondary or tertiary hospitals from 2010 to 2023. Patients were grouped by lipid-lowing therapy: statins group (n=549) and not taking statins group (n=811). The primary endpoint was MACCE, a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke, at 1 year. Secondary endpoints included cardiac death (CD), stroke, and recurrence of myocardial infarction at 1 year. Inverse probability treatment weighting (IPTW) based on propensity scores was performed to balance baseline characteristics. A multivariate adjusted Cox proportional hazard model evaluated the association between lipid-lowing therapy and clinical endpoints. Results Of the 1,360 patients, 77.2% were men, and the median age was 92 years. During 1 year follow up, 35.3% of patients experienced MACCE, and 28.7% died due to CD. After IPTW, the incidence of MACCE was lower in the statins group compared to the non-statins group (33.3% vs. 42.6%, p=0.036), as was 1- year mortality due to CD (26.2% vs.35.9%, p=0.021). However, there were no differences in the incidence of stroke (2.8% vs. 4.5%, p＞0.274) or recurrence of myocardial infarction (4.7% vs. 5.1%, p=0,855) at 1 year. Kaplan-Meier analysis showed a lower probability of 1-year MACCE and CD in the statins group (log-rank test, p<0.001). Multivariate Cox regression analysis demonstrated that statin therapy reduced the incidence of MACCE (aHR 0.67; 95%CI, 0.40–0.91; p=0.009) and 1-year CD (aHR 0.63; 95%CI, 0.45–0.87; p=0.005). Conclusions Lipid-lowering therapy with statins was associated with a significantly lower risk of 1-year MACEE and cardiac death in elderly patients aged over 90 years with AMI. These findings support the use of lipid-lowing therapy in elderly individuals.

Safety and efficiency of implementation of high-sensitivity troponin T in the assessment of emergency department patients with cardiac chest pain.

For emergency department (ED) patients with cardiac chest pain, introduction of high-sensitivity troponin (hsTnT) pathways has been associated with reductions in length of stay of less than 1h. At two urban Canadian sites, we introduced hsTnT on January 26, 2016. While the prior diagnostic algorithm required troponin testing at 0 and 6h, serial hsTnT serial testing was conducted at 0 and 3h. We identified consecutive patients who presented with cardiac chest pain from January 1, 2015, to March 31, 2017, along with 30-day outcomes. The primary outcome was a missed 30-day major adverse cardiac event, (MACE) defined as death, revascularization, or readmission for myocardial infarction occurring in a patient-discharged home with a minimizing diagnosis and without cardiac-specific follow-up. Secondary outcomes included admission rate, ED length of stay, and MACE. We compared pre- and post- implementation periods using descriptive methods and repeated this analysis in patients with noncardiac chest pain. We collected 5585 patients with cardiac chest pain, (2678 pre- and 2907 post-introduction) and 434 had (7.8%, 95% CI 7.1 to 8.5%) MACE, with 1 missed MACE. (0.2%, 95% CI 0.04 to 1.3%). Admission rate was stable at 24.1% pre- and 23.7% while median length of stay decreased from 464 to 285 min, a difference of 179 min. (95% CI 61 to 228 min). For 11,611 patients with noncardiac chest pain, admission rate (9%) and length of stay (191 versus 193 min) remained constant. Implementation of hsTnT for evaluation of ED chest pain patients was safe and associated with a 3-h decrease in length of stay.

Prognostic importance of persistent elevations in high-sensitivity troponin T in the early convalescent phase (two weeks) following high-risk myocardial infarction: insights from the PARADISE-MI trial

Abstract Introduction Myocardial infarction (MI) is defined by a rise and fall in cardiac troponin (cTn) with clinical evidence of acute myocardial ischemia. How often cTn remains elevated in high-risk patients stabilized following MI and the relation between convalescent cTn levels and subsequent clinical outcomes in these patients is unknown. Aims To evaluate the prognostic importance of high-sensitivity cTn T (hs-cTnT) in the early convalescent phase of a MI for a range of cardiovascular (CV) outcomes in patients enrolled in the Prospective ARNI vs ACE inhibitor trial to DetermIne Superiority in reducing heart failure Events after Myocardial Infarction (PARADISE-MI). Methods Patients ≥18 years without prior heart failure (HF) (n=5661) were randomized to sacubitril/valsartan or ramipril within 0.5 to 7 days of MI complicated by transient pulmonary congestion, LVEF ≤40%, or both. Hs-cTnT was measured using the Roche Elecsys Troponin T-high-sensitive assay in 1093 patients two weeks after randomization (median 2.6 weeks after the index MI). Associations between log (2)-transformed hs-cTnT and clinical outcomes were investigated in landmark analyses using Cox regression models adjusted for clinical covariates of known prognostic importance and NT-proBNP (Figure). Results Median week 2 hs-cTnT concentration was 34 ng/L [IQR 17-94 ng/L] and exceeded the 99th percentile upper reference limit in 69% of patients. Patients with persistently elevated hs-cTnT concentrations (n=753) were older, more likely men, more commonly had atrial fibrillation and lower estimated glomerular filtration rate and less likely had a prior MI. They more commonly had presented with ST-segment elevation MI and pulmonary congestion and had higher concentrations of NT-proBNP. Rates of primary reperfusion were similar. Log(2)-transformed hs-cTnT was only weakly correlated with LVEF (rho = -0.15, p<0.001), irrespective of the type of MI. hs-cTnT was independently and linearly associated with the primary composite outcome of CV death or incident HF (adj HR 1.17 per doubling; 95% CI, 1.03 – 1.34), all-cause death (adj HR 1.20; 95% CI, 1.01 – 1.44) and CV death (adj HR 1.25; 95% CI, 1.02 – 1.52) but not with non-CV death (adj HR 1.04; 95% CI, 0.70-1.54). hs-cTnT was not significantly associated with recurrent fatal or non-fatal MI (adj HR 1.00; 95% CI, 0.85-1.18) (Figure). Concentrations of week 2 hs-cTnT were not altered by sacubitril/valsartan relative to ramipril (+4%; 95% CI, -8% to 18%). Conclusions Persistent elevations in hs-cTnT during the early convalescent phase following high-risk MI are common and are associated with heightened risk of all-cause death, CV death and incident HF but not of recurrent MI or non-CV death. hs-cTnT measured ~2.5 weeks after high-risk MI provides incremental prognostic information beyond traditional risk factors and NT-proBNP.

Long-term prognosis after ST-elevation myocardial infarction according to the Canadian Cardiovascular Society classification of tissue injury severity in acute myocardial infarction

Abstract Background The recently proposed Canadian Cardiovascular Society (CCS) classification of acute myocardial infarction (MI) describes 4 stages of tissue injury identified by cardiac magnetic resonance imaging (CMR); 1) oedema without late gadolinium enhancement (LGE); 2) LGE without microvascular obstruction (MVO); 3) MVO; and 4) intramyocardial haemorrhage (IMH). Prior studies examining the relationship between these characteristics and outcomes are limited by variations in imaging and measurement techniques, in particular the distinction between MVO and IMH. The relationship between the proposed CCS classification of MI and outcomes has not been described. Purpose To explore the prognostic significance of the CCS classification of MI tissue injury in patients with ST-elevation MI (STEMI). Methods The British Heart Foundation MR-MI study was a prospective single-centre CMR cohort study in patients with STEMI (July 2011-November 2012). CMR was performed on a single Siemens MAGNETOM Avanto 1.5-Tesla scanner at 2 days post-STEMI. The imaging protocol included LGE and T2* mapping, allowing for the identification of infarct, MVO, and IMH. Follow-up for the occurance of major adverse cardiovascular events (MACE) (recurrent MI, ischaemic stroke and cardiovascular death) and a composite outcome of heart failure hospitalization/ICD implantation (HFH) or all-cause death was performed via electronic case note review. Results 246 patients had complete data for this analysis. Of these, 6 (2%) were CCS Stage 1, 105 (43%) were Stage 2, 33 (13%) were Stage 3, and 102 (41%) were Stage 4. Due to the low number in CCS stage 1, these patients were pooled with Stage 2 for the purposes of this analysis (CCS Stage 1/2). Average age was 58 (SD 11) years and 188 (76%) were male. With higher CCS stage, more patients were Killip class III/IV at presentation, had the LAD as culprit artery and had TIMI flow 0/1 pre-PCI. Patients with higher CCS stage had higher peak troponin-I and NT-proBNP, lower left ventricular function, higher left ventricular volumes and larger infarct size (Table). Median follow-up was 11.8 years. HFH or all-cause death occurred in 80 (33%) patients (22 HFH and 58 all-cause deaths), and MACE occurred in 63 (26%) patients (41 recurrent MI, 11 ischaemic stroke events, and 11 cardiovascular deaths). There were no significant differences in outcomes between CCS Stage 3 and CCS Stage 1/2 (Figure). Patients with CCS Stage 4 had a higher risk of HFH or all-cause death (HR 1.73, 95%CI 1.08-2.77; p=0.022) and MACE (HR 1.88, 95%CI 1.10-3.20; p=0.021) as compared with those in CCS Stage 1/2 (Figure). Conclusion The novel CCS classification of MI tissue injury identifies patients at the highest risk of adverse outcomes following STEMI. The relationship between the presence of IMH (CCS Stage 4) and adverse outcomes highlights the importance of T2* imaging in post-MI CMR protocols in order to identify this prognostically important biomarker.

Overview of the risk of myocardial infarction in patients with aortic stenosis: insights from the VALVENOR Registry

Abstract Background Close interaction between aortic stenosis (AS) and coronary artery disease (CAD) has been suggested. However, the risk of myocardial infarction (MI) in patients with AS is poorly described outside the context of aortic valve replacement. Objectives To assess the incidence, correlates and impact on outcomes of MI occurrence in patients with different degrees of AS severity. Methods Between 2016 and 2017, the multicenter prospective VALVENOR registry enrolled 2,830 outpatients with native valvular AS (peak aortic jet velocity (Vmax) ≥ 2.5m/s). AS was defined as mild (Vmax 2.5-2.9), moderate (Vmax 3-3.9) or severe (Vmax ≥4). MI was defined using the 4th universal definition (type 2 MI were not considered). Results The mean age was 76.0 years, 54% of the patients were men and 18.3% had experienced prior coronary event (PCE). Altogether, one third (n=820 [30.3%]) of the patients had diabetes. At 5 years, the cumulative incidence of MI (death as competing event) was only 2.5% (n=72, 1/3 of ST-elevation MI). Sixty MI (83.3%) were categorized as type 1 MI while 12 were peri-procedural MI (surgical aortic valve replacement, n=5; transcatheter aortic valve replacement, n=2; coronary artery bypass surgery, n=1; percutaneous coronary intervention, n=3; coronary angiography, n=1). PCE and angina symptoms were associated with an increased risk, whereas female gender with a decreased risk. By contrast, AS severity was not associated with the risk of MI. Five-year cumulative incidence of MI was 6.5% [95% CI, 4.5 - 8.9] in patients with PCE vs. 1.7% [95% CI, 1.2 - 2.3] in patients with no PCE (P<0.001), 8.3% [95% CI, 4.1 - 14.4] in patients with angina vs. 2.3% [95% CI, 1.8 - 2.9] in patients without angina (P<0.001), and 3.2% [95% CI, 2.4 - 4.2] in men vs. 1.8% [95% CI, 1.1 - 2.6] in women (P=0.014). Subsequent mortality was high and at 52.8% during follow-up (median 648 days after MI occurrence). When analyzed as a time-dependent variable, incident MI was a powerful predictor of mortality (HR=2.00, P<0.001 after adjustment). Conclusions In patients with AS, the risk of MI is relatively low especially in patients without PCE and without angina. No association between the risk of MI and AS severity was observed. Although rare, incident MI is strongly associated with subsequent mortality.

Cost-effectiveness of semaglutide for secondary prevention of cardiovascular disease in the United States

Abstract Background In the SELECT trial, semaglutide produced a 20% reduction in the composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke in individuals with overweight or obesity who did not have diabetes but had established pre-existing cardiovascular disease (CVD). Cost is an important barrier to widespread uptake of semaglutide, particularly in the US, and the cost-effectiveness for the secondary prevention of CVD is uncertain. Purpose To evaluate the cost-effectiveness of semaglutide vs. no obesity treatment for the secondary prevention of CVD from a US healthcare sector perspective. Methods The CVD Policy Model is an established, validated simulation model of fatal and non-fatal CVD outcomes and costs in the US population. Using data from the National Health and Nutrition Examination Survey, we created a nationally representative cohort of SELECT-eligible individuals (age ≥45, BMI ≥27kg/m2, no diabetes, pre-existing CVD). Healthcare costs associated with acute and chronic CVD were estimated from national survey and claims data and inflated to 2023 US dollars. The simulated control arm received usual care; the intervention arm received weekly semaglutide 2.4mg injections (assuming 8% discontinuation, which occurs year one). We reproduced the effectiveness of semaglutide based on results of the SELECT trial primary cardiovascular composite endpoint (non-fatal MI, non-fatal strokes and CVD death). The base case assumed 7% of patients receiving semaglutide developed injection-site reactions. Monthly cost of semaglutide was assumed to be $717 (US price net of rebates and discounts), but this was varied in sensitivity analyses. The analysis adopted a health system perspective over lifetime horizon. Results Approximately 4.7 million US adults would meet SELECT trial eligibility criteria. Over a lifetime horizon, semaglutide is projected to avert 538,000 major adverse cardiovascular events (241,000 nonfatal MIs; 80,000 nonfatal stokes, and 217,000 cardiovascular deaths) at an incremental cost of $613 billion. The incremental cost effectiveness ratio for semaglutide was $443,000 per quality-adjusted life year (QALY) gained. In order to meet cost-effectiveness thresholds of $50,000/QALY, $100,000/QALY, $150,000/QALY, drug costs would have to decline 90%, 79%, and 69% respectively. In sensitivity analyses, lowering drug cost to the current UK price (~ $220 per patient per month) would improve the incremental cost-effectiveness of semaglutide to <$150,000 per QALY gained, a potential upper threshold for cost-effectiveness in the US. Conclusion Widespread uptake of semaglutide in the SELECT-eligible U.S. population would prevent a large number of cardiovascular events, but its use would be low economic value at current US prices. Lowering prices in line with those in Europe (e.g., monthly price from $717 to $223) would make the therapy cost-effective at a threshold of $150,000 per QALY gained.

Lower rate of ischemic events with PCSK9 inhibition in patients with atherosclerotic cardiovascular disease but without prior ischemic events

Abstract Background Individuals with atherosclerotic cardiovascular disease (ASCVD) without prior ischemic events, such as myocardial infarction (MI), ischemic stroke (IS), or unstable angina (UA) hospitalization, are at very high risk for having an event. Purpose To estimate the impact of PCSK9 inhibitor (PCSK9i) therapy on ischemic events in this population. Methods Patients with ASCVD were initially selected from the Optum Research Database during Jan 2016 to Dec 2022. For selected patients the index (time zero for follow-up) was required to be in a period of ASCVD without prior ischemic events, however patients may have ischemic events after index. Determination of ASCVD and ischemic events was based on diagnosis and procedure codes. For the PCSK9i group, index was initiation of PCSK9i and information before index was examined to ascertain ASCVD and rule out prior ischemic events. For each patient in the PCSK9i group, up to 5 matching patients in the no-PCSK9i group were chosen based on propensity score (PS) distance, with maximum allowable PS distance of 0.1. Among all possible choices for index for the no-PCSK9i patient, the selected one minimized the PS-distance. The primary endpoint was defined as the composite of nonfatal MI, nonfatal IS, and all-cause death. In order to further reduce bias and ensure causally interpretable estimation, the G-computation methodology was employed by marginalizing the conditional treatment effect (as estimated by a Cox model) over the baseline characteristics. Two effects were estimated: intention-to-treat (ITT) where only the treatment assignment at index was considered as the intervention, and per-protocol (PP) where the effect of sustained treatment with PCSK9i over time was estimated. Results A total of 15,067 and 66,470 patients met the selection criteria for the PCSK9i and no-PCSK9i groups, respectively. Baseline characteristics were well-balanced at index. G-computation analysis resulted in estimated survival curves over time in the two groups for the ITT and PP scenarios (Figures 1 and 2). For the ITT scenario, the estimated 5-year event rate was 18.7% (95% confidence interval [CI]: 17.1%–20.1%) in the PCSK9i group and 28.4% (95% CI: 27.7%–29.1%) in the no-PCSK9i group. The implied relative risk reduction (RRR) and absolute risk reduction (ARR) were 34.3% (p<0.001) and 9.7% (p<0.001), respectively, in favor of the PCSK9i group. For the PP scenario, the estimated 5-year event rate was 10.7% (95% CI: 9.7%–11.7%) in the PCSK9i group and 28.8% (95% CI: 28.3%–29.5%) in the no-PCSK9i group. The implied RRR and ARR were 62.7% (p<0.001) and 18.1% (p<0.001), respectively, in favor of the PCSK9i group. Conclusions Initiation of PCSK9i in patients with ASCVD but without prior ischemic events is associated with significantly and substantially lower risk for ischemic events.Event Rates Intention-to-Treat ScenarioEvent Rates Per-Protocol Scenario

Unleashing the potential: early evaluation of blood pressure control with novel measurements in patients with hypertension

Abstract Objective To assess the prognostic value of two novel blood pressure measurements——short-term cumulative systolic blood pressure (SBP) load and Time in Target Rang (TTR) in major adverse cardiovascular outcomes and all-cause mortality. Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 90-days follow-up were enrolled. Short-term cumulative SBP load and TTR were calculated by the 3-month SBP values in the follow-up period (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs), defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Secondary outcomes were the components of the primary outcomes and all-cause mortality. Results The study population included 8639 adults (median [IQR]or mean (%) baseline age, 67 [61,76] years; 2940 women (35.1%); Median follow-up time 3.8[3.3-4.4] years). 559 MACEs were occurred. Participants categorized by tertiles of cumulative SBP Load (T1: [0,0.1572]; T2: (0.1572 ,3.5946]; T3: (3.5946 ,30.2949]) showed a significant increase hierarchical trend (P for trend <0.05) in the incidence of MACEs and stroke. For Participants grouped by SBP TTR (T1: [0,21.2657]; T2: (21.2657 ,71.1462]; T3: (71.1462 ,100]), it indicated a decrease hierarchical trend (P for trend <0.05) in the incidence of MACEs and MI (Fig2 and Fig3). Both short-term cumulative SBP Load (HR: 1.117(1.033-1.208)) and TTR (HR: 0.861(0.785-0.945)) were correlated with MACEs independently(tabal1). According to C-statistics and Net Reclassification Indexes (NRI), short-term cumulative SBP Load and TTR both outperformed mean SBP and SBP standard derivation (SD) on the prognosis value of MACEs. Moreover, our results showed that the coefficient of cumulative SBP Load under penalty decreased to 0 with the largest log(lambda),which indicted a major role across 4 different measures in models. (Fig 4). Conclusions Both short-term cumulative SBP load and TTR had an independent prognosis value for MACEs superior to mean SBP and SBP SD in hypertension patients without diabetes. This study provided the evidence of novel BP measurements for early assessment of BP levels after antihypertensive treatment.

Effects of deferment of clinic visit on cardiovascular outcomes during COVID-19 outbreak: a prospective cohort study

Abstract Background Current guidelines recommend 3-6 months interval outpatient follow-up for patients with cardiovascular (CV) diseases and risk factors such as hypertension, diabetes mellitus (DM) and dyslipidemia. The impact of longer follow-up intervals is unclear. From 2020 to 2022, due to the infection control measures for COVID-19 pandemic, many patients voluntarily deferred their scheduled clinic visits. This provided us with an opportunity to study the impact of prolonged visit intervals on management CV risk factors. Purpose We aimed to investigate the impact of prolonged clinic visit intervals on CV outcomes and CV risk factor management among patients with CV diseases. Methods Patients with at least 1 CV risk factor (DM, hypertension, dyslipidemia, or a history of CV disease) were recruited from cardiology outpatient clinics from a tertiary teaching hospital from 2020-2022. Patients who opted to defer their appointment (Deferred group) were compared to those who attended their scheduled appointment (Normal group). The primary outcomes were composite major adverse cardiovascular events (MACE) of myocardial infarction, stroke, or CV-related death. The secondary outcomes were any unscheduled hospitalizations, suboptimal DM control (haemoglobin A1C >7%) or hyperlipidemia (LDL > 1.4 mmol/L). Results Out of the 455 patients recruited from outpatient clinics, 162 patients (35.6%) opted to defer their scheduled clinic visit (mean age 64.7 ± 12, 37.7% female), and 293 patients (mean age 64.5 ± 10, 36.2% female) continued to attend their appointments. The mean appointment interval was 226 days for the normal group and 582 days for the deferred group (p< 0.001). There was no significant difference in the primary outcome of MACE between the ‘Normal’ group and the ‘Deferred’ group (2.5% vs 0.6%, p=NS). The number of patients with suboptimal DM control (11.4% vs 21.9%, p = 0.029) was higher in the deferred group, whereas suboptimal hyperlipidemia (73.1% vs 77.1%, p=NS) was not statistically different. There were a total of 27 of unscheduled hospitalizations, among which the majority was for CV-related events (63.0%). Patients in the ‘Deferred’ group had higher rates of unscheduled hospitalization (12.3% vs 2.4%, p < 0.001) and higher rate of CV-related hospitalization compared to the ‘Normal’ group (6.2% vs 2.4%, p=0.041). Conclusion Our prospective data demonstrates that a prolonged clinic visit interval of more than 365 days was not associated with significant increase in adverse CV event or worsening of lipid control. However, prolonged clinic visit interval was associated with worse DM control and more frequent unscheduled hospitalization. More frequent medical contact might allow timely management of medical emergency at the outpatient setting and contribute to the lower rate of hospitalization in the routine follow-up group.

Obesity paradox, weight-free anthropometric measures, and major adverse cardiovascular events in the elderly: Insight from the Northern Shanghai Study

Abstract Aims Many studies have investigated the obesity paradox in the elderly. However, besides body mass index (BMI), many other anthropometric measures, such as the waist-to-hip ratio (WHR), provide a better indication of body fat distribution and may be more useful in a geriatric population. Methods 3285 participants aged over 65 years old from the Northern Shanghai Study were included in this analysis. Eight anthropometric measures, including weight-related measures (BMI, weight-adjusted-waist index, body shape index and body surface area) and weight-free measures (WHR, waist-to-height ratio, body roundness index, relative fat mass) were measured and calculated with standard methods. Major adverse cardiovascular events (MACEs) included the non-fatal myocardial infarction, non-fatal stroke or cardiovascular death. Results Participants had an average age of 71.4 years and 1428 (43.47%) were men. The median follow-up was 5.4 years (IQR, 4.4-7.3 years) and 218 events occurred. Participants with obesity (BMI ≥ 28 kg/m2) were associated with a higher risk of MACEs compared with the normal (adjusted Hazard ratio = 1.54, 95% confidence interval (CI): 1.07-2.22, P=0.020). Restricted cubic splines also highlighted the robust correlation between high BMI and high MACEs risk (Pfor overall=0.025, Pfor nonlinear=0.339). Similarly, the aHR for the incidence of MACEs in WHR quartile 4 versus quartile 1 was 1.96 (95% CI: 1.26-3.05, P=0.003). When WHR was examined as a continuous variable, the result remained unaltered (Pfor overall=0.020, Pfor nonlinear=0.353). In adjusted model, all four weight-free measures were significantly associated with increased risk of MACEs (all P<0.05), while only two weight-related measures were related to the risk of MACEs. Conclusion In the elderly, BMI and alternative anthropometric measures showed no evidence of an "obesity paradox". Weight-free measures were more relevant to a risk of MACEs.Take home message

Prognostic significance of coexistent coronary artery disease in patients undergoing transcatheter aortic valve implantation for aortic stenosis

Abstract Background The optimal management of coronary artery disease (CAD) in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) is uncertain. As TAVI expands into lower risk cohorts with longer life expectancies there is increasing need to determine the prognostic significance of coexistent CAD and identify which lesions may benefit from revascularisation. Purpose To evaluate the prognostic significance of coexistent CAD in patients with AS undergoing TAVI stratified according to myocardial territories at risk. Methods Using a retrospective, single-centre, observational registry, patients undergoing TAVI for severe AS between 2015 and 2020 were included. CAD was angiographically determined using computed tomography or invasive coronary angiography. CAD was stratified into 1) low-risk: <70% stenosis in all major epicardial coronary arteries or <50% in the left main (LM); 2) intermediate-risk: ≥70% stenosis in one or two arteries, except the proximal left anterior descending (LAD) and LM; 3) high-risk: ≥70% stenosis in the proximal LAD, ≥70% stenosis in 3 arteries or LM stenosis ≥50%. Patients with previous CABG were categorised as high-risk if: ≥70% stenosis of 3 coronary grafts or graft supplying a proximally stenosed LAD; and intermediate-risk if: ≥70% stenosis of 1 or 2 non-LAD grafts. Baseline characteristics and procedural outcomes were compared between the 3 cohorts, with the impact of CAD on outcomes evaluated after adjustment for demographics and comorbidities. Results 1805 patients were included; median age 84 (79-88), 51% male sex, median logistic Euroscore 13 (8-21). 1281 (71%), 384 (21%) and 140 (8%) patients were characterised as low-, intermediate- and high-risk coronary anatomy respectively. High risk patients were older than the other groups, however, did not have the highest prevalence of comorbidities (Table 1). Other than pacemaker implantation (9% vs 12% vs 6%, p=0.04), there were no differences in procedural complications or in-hospital mortality between groups (Table 1). At a median follow-up of 3.5 (2.3-4.8) years, 920 patients (51%) died, 292 (16%) had hospitalisation for heart failure (HHF) and 565 patients (31%) had a major adverse coronary event (MACE); defined as either myocardial infarction, HHF or cardiovascular death. Coronary anatomical stratification was associated with MACE (Log rank p<0.001) (Figure 1). After multivariate adjustment, high-risk anatomy was associated with all-cause mortality (hazard ratio (HR): 1.34, 95% confidence interval (CI): 1.06-1.68, p=0.013), HHF (HR: 1.49, 95% CI: 1.01-2.21, p=0.046) and MACE (HR: 1.68, 95% CI: 1.27-2.21, p<0.001). Conclusions Whilst the presence of CAD does not impact TAVI procedural safety, untreated high-risk coronary anatomy is associated with future adverse events and may warrant intensive medical therapy and/or revascularisation.

Red cell distribution width as a predictor of cardiovascular events in high-risk patients with statin intolerance: post-hoc analysis of the CLEAR Outcomes trial

Abstract Background Despite optimal lipid-lowering therapy there is up to 70% residual risk of recurrent atherosclerotic cardiovascular disease (ASCVD) events, motivating further testing of alternative risk factors and disease pathways. Red cell distribution width (RDW) is a simple and reproducible marker of heterogeneity of cell size in the peripheral blood. High RDW is associated with an increased risk of ASCVD and death, independent of established risk factors. Recent data suggest no significant impact of PCSK9 inhibitors on hsCRP or RDW. In CLEAR Outcomes, baseline hsCRP predicted risk for future cardiovascular (CV) events and death more strongly than elevated LDL-C. It has been shown that bempedoic acid (BA) reduces hsCRP, but its effects on RDW are unknown. Purpose To analyze the effect of BA on a 4-component composite of incident myocardial infarction, stroke, coronary revascularization, or cardiovascular death (MACE-4) and for CV death by baseline RDW, and to confirm the association of increased RDW with elevated risk of MACE. Methods A total of 13,970 individuals with statin intolerance, with or at high risk for ASCVD, were randomized in the multinational CLEAR Outcomes trial with a median follow up of 3.4 years. Compared to placebo, BA reduced mean LDL-C by 21% and median hsCRP by 22% at 6 months. Quartiles of increasing baseline RDW were assessed as predictors of future adverse events after adjustment for traditional risk factors, hsCRP, and randomized treatment assignment. Results Compared to placebo, BA reduced mean RDW by 0.28% at 6 months and 0.13% at 36 months (p<0.0001). There was a weak positive correlation between hsCRP and RDW at baseline (Figure 1). In the placebo group, higher baseline RDW was associated with an increase in the likelihood of MACE-4 and CV death, and the hazard ratios (HR) associated with a 1% increase in RDW after adjusting for covariates and hsCRP were 1.06 (95% CI 1.02-1.11) and 1.22 (1.15-1.29), respectively. When grouped by quartiles of baseline RDW, compared with a reference group with lowest RDW (<13.7%), there was a notable increase in the risk of MACE-4 and CV death among the higher quartiles in the placebo group (Table 1). Those in the 4th quartile demonstrated a 3-fold increase in the risk of CV death (HR, 3.03, 2.00-4.60). The adjusted HRs (95% CI) for BA vs placebo for MACE-4 were generally lower in individuals with elevated baseline RDW than in those in the first quartile [Q1: RDW≤13.7%; 0.96 (0.79-1.17), Q2: RDW 13.7%-14.4%; 0.81 (0.67-0.97), Q3: RDW 14.4%-15.2%; 0.90 (0.75-1.09), and Q4: RDW>15.2%; 0.84 (0.7-1.01)]. Conclusions In a large randomized controlled clinical trial setting, we confirmed an association between elevated RDW and MACE-4. Compared with placebo, BA demonstrated efficacy in reducing CV risk in patients with moderately increased RDW.Figure 1.Correlation of hsCRP and RDWTable 1.Risk of Outcome by RDW Quartile

Residual risk post acute coronary syndroms after 1 year of cardiac rehabilitation. Can we improve it?

Abstract How much do we reduce residual risk with a cardiac rehabilitation program? What is left to do? Which would be the impact of a lower cholesterol threshold for the use of more potent lipid lowering drugs on residual risk? We explored these issues. Methods We retrospectively analyzed clinical and biochemical data from patients after 1 year of cardiac rehabilitation following an acute coronary event. Changes in residual risk of combined myocardial infarction, stroke and cardiovascular death, and its modification with optimization of treatment in patients with suboptimal lipid control, and with the use of PCSK9 inhibitors in those with a LDL-cholesterol over 70 mg/dl, were estimated using the SMART-REACH model calculator. Wilcoson and McNemar tests for paired-samples were used in the statistical análisis. Results 262 consecutive patients were included. Median age was 63.5 years, 80.5% men, 89.3% stented. Baseline use of high intensity statins was 90.8%. After 1 year, the use of Ezetimibe was doubled to 77.1%, empaglifozin to 26%, and PCSK inhibitors were used only in 5%, with a residual use of colchicine. Blood pressure and Cholesterol profile improved after 1 year, with no change in HbA1c. Absolute 10- years and life-long residual risk were reduced 4.8% (95%CI:3.6-5.9) and 6% (95%IC: 4.5-7.5) respectively (both p<0.001). LDL-cholesterol was >55 mg/dl with a suboptimal lipid lowering treatment in 29.8% of patients: an optimization to higher dose of rosuvastatin/atorvastatin plus ezetimibe would decrease absolute 10-years and life-long residual risk in 7.2% (95%CI: 4.9-9.4) and 9.9% (95%CI: 6.4-13.5%) respectively (both p<0.001). LDL-cholesterol remained > 70 mg/dl after higher dose of statin plus ezetimibe in 13.7% of patients: use of PCSK9 inhibitors in this group would reduce absolute 10-year and life-long residual risk in an additional 5.4% (95%CI:2.4-7,6;p=0,018) and 7% (95%CI: 3,8-10,1) compared to maximal dose of statins plus ezetimibe. Conclusions Cardiac rehabilitation programs reduce cardiac risk 1 year after an acute coronary event. Residual risk remain very high, and a significant proportion of patients do not reach recommended targets and optimal lipid lowering treatment. Optimization of lipid lowering drugs, and a lower LDL-cholesterol threshold for the use of PCSK9 inhibitors, would have a significant impact on residual risk.Changes in residual riskPCSK9-inhibitors in LDLchol >70 mg/dl

Trends in major cardiac events after ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention from 2003 to 2017: the western Denmark heart registry

Abstract Background In Denmark, primary percutaneous coronary intervention (PCI) has been the national reperfusion strategy since 2003. We recently reported a gradual decline in 1-year mortality in patients treated with pPCI-treated STEMI from 2003 to 2017. To elucidate potential causes of this observation, we examined temporal trends in the 1-year risk of major adverse cardiovascular events (MACE). Purpose To examine trends in 1-year risks of MACE following STEMI treated with pPCI from 2003 to 2017. Methods Using the Western Denmark Heart Registry, we identified STEMI patients undergoing first-time pPCI from 2003 to 2017 and divided the patients into four time periods. The main outcome was 1-year risk of MACE, defined as recurrent myocardial infarction, ischaemic stroke, or cardiovascular death. Cause-specific adjusted hazard ratios (HR) were used to assess temporal trends using the first period (2003-2006) as reference. Further, temporal trends were compared to an age-, sex-, and calendar-year matched general population. Results From 2003 to 2017, 18,540 pPCI-treated STEMI patients were identified (median [Q1-Q3] age, 64 [55-74] years); 13,639 men [74%]). Trends in 1-year risk of MACE showed a gradual reduction over time from 13.0% in 2003-2006, 11.8% in 2007-2010, 9.7% in 2011-2014, to 8.7% in 2015-2017 (Figure). The adjusted relative risk reduction was 33% when comparing 2015-2017 with 2003-2006 (adjusted HR 0.67, 95% CI 0.58-0.76). Comparable relative risk reductions were observed for all three individual components of MACE of 33-35%. Compared to the matched general population, the 1-year risk difference in MACE decreased from 11% in 2003-2006 to 7% in 2015-2017. Conclusions In a high-income European country with a fully implemented pPCI strategy, 1-year risk of MACE declined by approximately one-third after first-time STEMI between 2003 to 2017. This MACE reduction was substantially larger than observed in the matched general population, i.e., confirming an important reduction in the excess risk associated with STEMI.

Symptomatic patients without coronary artery disease do not have excess cardiovascular risk compared to the general population

Abstract Background Patients with stable angina with no coronary atherosclerosis by coronary computed tomography angiography (CCTA) have a lower cardiovascular risk compared to CCTA patients with greater atherosclerotic burden. However, it remains unknown whether these symptomatic patients have excess cardiovascular risk when compared to the general population and if any excess risk is sex or age dependent. Purpose To examine the 10-year cardiovascular risk and mortality in patients with no coronary atherosclerosis by CCTA compared to a matched general population comparison cohort. Methods We included every symptomatic CCTA patient with no coronary artery disease (CAD), defined as no coronary plaques and Agatston calcium score of 0, in Western Denmark from 2008-2021. Each patient was matched by age and sex with 5 individuals with no previous history of ischemic heart disease from the Western Danish general population. Maximum follow-up was 10 years. Outcomes were myocardial infarction, ischemic stroke, and all-cause death. We estimated 10-year risk difference (RD) and incidence rate ratios (IRR) using a conditional Poisson regression, comparing patients with no CAD to the general population cohort. Additionally, we performed age- (<45 year, 45-65 years, and ≥65 years) and sex stratified analyses. Results We included 39,223 patients with no CAD who were matched with 196,115 individuals from the general population. Median age was 54 and 60% were women. Baseline use of anti-thrombotic agents, statins, and anti-hypertensive drugs was higher in patients with no CAD than the general population. Median follow-up was 6.1 years. CCTA patients with no CAD had lower risk of myocardial infarction [RD -0.2%, IRR 0.75 (95% CI 0.65-0.85)] and death [RD -3.3%, IRR 0.51 (95% CI 0.48-0.55)], but similar risk of ischemic stroke [RD 0.0%, IRR 0.93 (95% CI 0.84-1.02)] compared to the general population (Figure 1). However, patients <45 years had higher 10-year risk of both myocardial infarction and ischemic stroke despite absence of CAD by CCTA compared the general population (Figure 2). Conclusions Symptomatic patients without CAD by CCTA do not have excess cardiovascular risk when compared to a general population cohort without known ischemic heart disease. Future cardiovascular risk management of these patients should therefore follow primary prevention guidelines. However, patients <45 years did exhibit higher risk of ischemic outcomes and may require intensified preventative treatment.Figure 1Figure 2

Impact of global longitudinal strain and anemia for predicting cardiovascular mortality in patients hospitalized for acute heart failure with atrial fibrillation

Abstract Background Iron deficiency is a prognostic factor in heart failure (HF) with reduced ejection fraction (EF). In patients with atrial fibrillation (AF) and HF, left ventricular EF (LVEF) measurements are imprecise due to irregular tachycardia, but it is unclear whether global longitudinal strain (GLS) and anemia assessment are prognostic. Purpose We examined whether GLS and anemia predict cardiovascular death (CD) in patients with acute HF complicated by AF. Methods We retrospectively enrolled patients aged 18 years or older with acute HF complicated by AF who were consecutively admitted to our hospital from January 2014 to December 2018. Exclusion criteria were acute coronary syndromes, no transthoracic echocardiogram performed within 30 days before or after admission, and missing data. All patients were followed up from admission to CD (due to myocardial infarction, HF, stroke or sudden death), or were censored at the date of last contact or 3 years. Anemia was defined as hemoglobin < 12 g/dL in females and hemoglobin < 13 g/dL in males. Patients were divided into four groups according to median GLS and anemia status. Results A total of 320 patients (mean age 79 ± 12 years, 163 females) were included in the analysis. The median duration of AF was 1.2 years; 11% (36/320) had paroxysmal AF. The median brain natriuretic peptide value was 623 pg/ml, and 52% of the patients (165/320) were in New York Heart Association functional class 4. During a median follow-up of 528 days, 24% (77/320) patients were observed with CDs: 2 myocardial infarctions, 51 HF-related deaths, 6 strokes, and 18 sudden cardiac deaths. At the 3-year follow-up, the survival rate by the Kaplan-Meier curve was 89% (95% confidence interval (CI) 76%-95%) in the no anemia group with high GLS (< -10%) and 40% (95% CI 25%-54%) in the anemia group with low GLS (≥ -10%) (p < 0.001, log-rank test). In multivariate Cox regression analysis, GLS (adjusted hazard ratio (aHR) 1.06, 95% CI 1.01-1.14, p = 0.017) and hemoglobin (aHR 0.85, 95% CI 0.76-0.96, p = 0.009) were independent factors for CD, with a significantly increased risk in the anemia group with low GLS compared to the no anemia group with high GLS (aHR 4.11, 95% CI 1.59-10.6, p = 0.004). The results were consistent with no interaction by gender or LVEF 50%. Conclusions Anemic patients with low GLS with AF and HF may have poor prognosis. Prospective studies are needed to determine whether iron supplementation improves prognosis in such patients.