Temporal Trends, Patient Characteristics, and Outcomes of Type 2 Versus Type 1 Myocardial Infarction Among Medicare Beneficiaries.

We investigated temporal trends in major cardiovascular events following first-time myocardial infarction (MI) and trends in revascularization and pharmacotherapy from 2000 to 2017. Using nationwide registries, we identified 120833 Danish patients with a first-time MI between 2000 and 2017. We investigated 30-day and 1-year mortality and the 1-year risk of first-time admission for heart failure (HF) and recurrent MI. Patients were younger with a higher prevalence of hypertension and diabetes in 2015-2017 compared with 2000-2002. The patients were predominantly male (65.6%), and the median age declined by 3 years through the periods. Percutaneous coronary interventions within 7 days after first-time MI increased significantly (2000: 11.4%vs. 2017: 68.6%; Ptrend<0.001). Cardiovascular medication after first-time MI changed significantly in the same period. Absolute risks and adjusted rates of outcomes were significantly lower in 2015-2017 compared with 2000-2002: 30-day mortality: 6.5%vs. 14.1% [hazard ratio (HR) 0.52, 95% confidence interval (CI): 0.48-0.55); 1-year mortality 10.7%vs. 21.8% (HR 0.52, 95% CI: 0.50-0.55); recurrent MI: 4.0%vs. 7.8% (HR 0.56, 95% CI: 0.51-0.62); and first-time admission for HF: 2.9%vs. 3.7% (HR 0.82, 95% CI: 0.73-0.92). The rates of 30-day/1-year mortality and recurrent MI showed significantly decreasing trends (Ptrend<0.001). The rates of first-time admission for HF were borderline significant (Ptrend=0.045). From 2000 to 2017, we observed a decreasing risk of recurrent MI, first-time admission for HF, and all-cause mortality in patients with a first-time MI. In the same period, we observed a high rate of guideline-recommended pharmacological treatment after first-time MI as well as increasing rate of early revascularization in Denmark. The results from the current study portrait the risk of all-cause mortality, recurrent MI, and first-time admission for HF in a real-life setting with a very high utilization of early revascularization and guideline-recommended pharmacological therapy. We observed a temporal trend of improved survival, reduced risk of recurrent MI, as well as reduced risk of first-time admission for HF after first-time MI from 2000 through 2017. We observed an increase in the overall use of revascularization, as well as early revascularization and use of guideline-recommended pharmacotherapy. Our study reveals important results from real-life, nationwide data, showing a reduced risk of cardiovascular outcomes after first-time MI during the past 20 years. Current guidelines are based on results from clinical trials. Our real-life results add additionally important knowledge on patients' prognosis after first-time MI and underline the importance of treating MI according to guideline recommendations.

Statin Intolerance and Risk of Coronary Heart Events and All-Cause Mortality Following Myocardial Infarction

Myocardial infarction (MI) is an acute cardiovascular disease that can increase prognosis risks such as arrhythmia, heart failure, shock, etc. Studies have found that even well-controlled coexistence of cancer could affect the quality of life in MI patients. However, the prognostic impact of cancer on MI patients is controversial. This meta-analysis aimed to assess the influence of cancer on the risk of future all-cause mortality, cardiovascular mortality, and major adverse cardiovascular and cerebrovascular events (MACCE) in MI patients. The Embase, PubMed, and Cochrane libraries were searched for cohort studies and case-control from inception to May 2022. The quality of the included pieces of literature was assessed using the Newcastle-Ottawa Quality Assessment Scale (NOS). All statistical analyses were performed using Stata statistical software versions 14.0 and 16.0. Sensitivity analysis assessed the robustness of the results, and funnel plots and Egger's tests evaluated the publication bias. A total of 10 studies were included, covering 7,210,530 participants. Summary analyses show that compared with non-cancer patients, cancer increased the risk of long-term all-cause mortality in MI patients (HR 1.58, 95% CI 1.36-1.84, I2 = 94.2%). However, no significant difference was observed in the risk of cardiovascular mortality (HR 1.18, 95% CI 0.91-1.54, I2 = 52.4%) or MACCE (HR 1.26, 95% CI 0.94-1.70, I2 = 99.2%). In subgroup analysis, cancer was associated with the risk of recurrent MI (HR 1.18, 95% CI 1.03-1.34, I2 = 88.8%), and major bleeding (HR 2.01, 95% CI 1.60-2.52, I2 = 93.1%), with no significant difference in the risk of stroke (HR 1.11, 95% CI 0.97-1.27, I2 = 85.1%). This meta-analysis shows that cancer increases the risk of all-cause mortality, recurrent MI, and major bleeding in MI patients but is not associated with the risk of cardiovascular death. Therefore, comprehensive multidisciplinary management and monitoring of potential future adverse events in MI patients with cancer are needed. The meta-analysis was registered in the International Register of Prospective Systematic Reviews (NO. CRD42022332775).

Current guideline statements for primary and secondary prevention of cardiovascular disease (CVD) rely on estimates of absolute risk of coronary events. For example, the American Heart Association guidelines on primary prevention state that persons with ≥10% risk over 10 years of myocardial infarction (MI) or coronary death should be considered for antiplatelet therapy with aspirin.1 Similarly, the National Cholesterol Education Program Adult Treatment Panel III (ATP III) guidelines2 state that target low-density lipoprotein level should be based on projected absolute risk of future coronary events rather than on presence or absence of specific risk factors. These guidelines state that patients at high risk of MI and coronary death, defined as an absolute 10-year risk of ≥20%, should have a target low-density lipoprotein level <100 mg/dL and should receive statin therapy if needed to achieve this goal. Stroke, however, is not included as one of the outcomes contributing to these absolute risk levels. Included in the group of patients with elevated risk, moreover, are those who already have ischemic heart disease, as well as patients deemed to be “coronary heart disease (CHD) risk equivalents,” indicating those at the same elevated risk as patients with ischemic heart disease. CHD risk equivalents include patients with diabetes mellitus, those with multiple risk factors that put them at elevated risk based on calculation of their Framingham Score, and patients with “other forms of symptomatic atherosclerotic disease.” The latter group is further defined to include those with peripheral arterial disease (PAD), abdominal aortic aneurysm (AAA), and carotid artery disease. The category of “risk equivalents” in the ATP III guidelines, however, does not include the vast majority (≈80%3) of ischemic stroke patients without carotid artery disease as cause of their stroke. Ischemic stroke is therefore notably excluded from the list of outcomes contributing to …

The benefit of extending clopidogrel treatment beyond the 12-month period recommended in current guidelines after myocardial infarction (MI) is debated. We analysed the risk of adverse cardiovascular outcomes after discontinuation of 12 months of clopidogrel treatment. This Danish retrospective nationwide study included all patients treated with clopidogrel after discharge from a first-time MI during 2004-09. The risk of death or recurrent MI after the discontinuation of clopidogrel was studied by multivariable Poisson regression models. Patients treated with and without percutaneous coronary intervention (PCI) were analysed separately. The follow-up was 18 months. Of the 29,268 patients included, 3214 (11.0%) experienced death or recurrent MI. There were 9819 (33.6%) patients treated only medically and 19,449 (66.4%) patients treated with PCI. Twelve months after the index MI, for patients treated only medically, the risk of death or recurrent MI in the first 90-day period of clopidogrel discontinuation was 1.07 (0.65-1.76; P= 0.79) [adjusted incidence rate ratio (IRR) and 95% confidence interval] compared with the next 90-day period of discontinuation. For patients treated with PCI, the corresponding IRR was 1.59 (1.11-2.30; P= 0.013). The risk of recurrent MI yielded an IRR of 0.77 (0.36-1.67; P= 0.51) for patients treated only medically and 1.87 (1.11-3.15; P= 0.019) for PCI-treated patients. Discontinuation of clopidogrel 12 months after MI is associated with an increased risk of death or recurrent MI in the first 90 days of discontinuation compared with the next 90-day period of discontinuation for patients treated with PCI, but not for patients not treated with PCI.

Diabetes is a potent risk factor for death and heart failure (HF) hospitalization following myocardial infarction (MI). Whether diabetes modifies the relationship between left ventricular ejection fraction (LVEF) and outcomes in the post-MI population is unknown. The Valsartan in Acute Myocardial Infarction trial (VALIANT) enrolled 14 703 patients with acute MI complicated by HF, systolic dysfunction, or both. We compared the risk of death, HF hospitalization, and/or recurrent MI among patients with and without diabetes using Cox proportional hazards models. To assess the relationship between diabetes, LVEF and outcomes, we assessed the relative influence of baseline LVEF on outcomes in diabetic and non-diabetic patients. Totally, 11 325 subjects (3095 diabetics) with site-reported LVEF and known diabetes status were included. At any given LVEF, diabetes was associated with a higher risk of all-cause mortality [adjusted hazard ratio (HR) 1.37, 95% CI 1.25-1.51], death or HF hospitalization (adjusted HR 1.42, 95% CI 1.31-1.51), and death or recurrent MI (adjusted HR 1.36, 95% CI 1.24-1.48). Diabetes modified the relationship between LVEF and death or HF hospitalization (P for interaction = 0.0109), such that the association between diabetes and increased risk was greater in magnitude at higher LVEF. No interaction was noted between diabetes and LVEF on risk of all-cause mortality or death or recurrent MI. Diabetes is associated with a higher risk of death or HF hospitalization across the spectrum of LVEF in high-risk post-MI patients. The magnitude of reduction in risk of death or HF hospitalization associated with increasing LVEF is significantly attenuated among patients with diabetes when compared to patients without diabetes.

There are no well-established predictors of recurrent ischemic coronary events after an acute coronary syndrome (ACS). Higher levels of homocysteine have been reported to be associated with an increased atherosclerotic burden. The primary endpoint was to assess the relationship between homocysteine at discharge and very long-term recurrent myocardial infarction (MI). 1306 consecutive patients with ACS were evaluated (862 with non-ST-segment elevation ACS [NSTEACS] and 444 with ST-segment elevation myocardial infarction [STEMI]) discharged from October 2000 to June 2003 in a single teaching-center. The relationship between homocysteine at discharge and recurrent MI was evaluated through bivariate negative binomial regression accounting for mortality as a competitive event. The mean age was 66.8 ± 12.4 years, 69.1% were men, and 32.2% showed prior diabetes mellitus. Most of the patients were admitted for an NSTEACS (66.0%). The median (interquartile range) GRACE risk score, Charlson comorbidity index, and homocysteine were 144 (122-175) points, 1 (1-2) points, and 11.9 (9.3-15.6) μmol/L, respectively. In-hospital revascularization was performed in 26.3% of patients. At a median follow-up of 9.7 (4.5-15.1) years, 709 (54.3%) deaths were registered and 779 recurrent MI in 478 (36.6%) patients. The rates of recurrent MI were higher in patients in the upper homocysteine quartiles (p < 0.001). After a multivariate adjustment, homocysteine along its continuum remained almost linearly associated with a higher risk of recurrent MI (p = 0.001) and all-cause mortality (p < 0.001). In patients with ACS, higher homocysteine levels identified those at a higher risk of recurrent MI at very long-term follow-up.

In established ischemic heart disease, the relationship between lipoprotein(a) and new cardiovascular events showed contradictory results. Our aim was to assess the relationship between lipoprotein(a) and very long-term recurrent myocardial infarction (MI) after an index episode of ST-segment elevation acute myocardial infarction (STEMI). We included 435 consecutive STEMI patients discharged from October 2000 to June 2003 in a single teaching center. The relationship between lipoprotein(a) at discharge and recurrent MI was evaluated through negative binomial regression and Cox regression analysis. The mean age was 65 years (55-74 years), 25.5% were women, 34.7% were diabetic, and 66% had a MI of anterior location. Fibrinolysis, rescue, or primary angioplasty was performed in 215 (49.4%), 19 (4.4%), and 18 (4.1%) patients, respectively. The median lipoprotein(a) was 30.4 mg/dL (12-59.4 mg/dL). After a median follow-up of 9.6 years (4.1-15 years), 180 (41.4%) deaths and 187 MI in 133 (30.6%) patients were recorded. After a multivariate adjustment, the risk gradient of lipoprotein(a) showed a neutral effect along most of the continuum and only extreme higher values identified those at higher risk of recurrent MI (P = 0.020). Those with lipoprotein(a) values >95th percentile (≥135 mg/dL) showed a higher risk of recurrent MI (incidence rate ratio, 2.34; 95% confidence interval, 1.37-4.02; P = 0.002). Lipoprotein(a) was not related to the risk of mortality (P = 0.245). After an episode of STEMI, only extreme high values of lipoprotein(a) were associated with an increased risk of long-term recurrent MI.

Risk of All-Cause Mortality, Recurrent Myocardial Infarction, and Heart Failure Hospitalization Associated With Smoking Status Following Myocardial Infarction With Left Ventricular Dysfunction

Background Aspirin is mandatory in the acute phase after myocardial infarction (MI); however, the efficacy of aspirin for long-term secondary prevention is less established and may have changed with the addition of modern therapies and diagnostics methods. Purpose To investigate the effectiveness of adherence to long term aspirin therapy at different timepoints following MI. Methods Using Danish nationwide registries, we included patients ≥40 years with a first time MI undergoing percutaneous coronary intervention from 2004 through 2017, who were alive, not treated with anticoagulants, and had stayed adherent to aspirin at one year after the index event (Figure 1). We evaluated adherence to aspirin therapy as proportion of days covered (PDC) ≤80% and &amp;gt;80% at four landmarks (2, 4, 6, and 8 years after MI, respectively). At each landmark, patients were excluded from the analysis if they had suffered a recurrent MI or stroke, died, emigrated or were on anticoagulant or P2Y12-inhibitor therapy. The absolute and relative risks of a composite of death, recurrent MI, or ischemic stroke at 2 years from each landmark were calculated through multivariable logistic regression analysis with average treatment effect modelling standardized to the distribution of age, sex, diabetes, hypertension, hypercholesterolemia, chronic kidney disease, cancer, peptic ulcer, former bleeding, and chronic obstructive pulmonary disease (as a proxy for smoking). Non-CVD death was used as a neutral comparator. Results A total of 40,114 individuals were included in the analysis. Suboptimal adherence to aspirin (PDC≤80%) increased from 10% at first landmark 2 years after MI to 19% at fourth landmark 8 years after MI (Figure 1). The standardized absolute risk of death, recurrent MI, or ischemic stroke was highest at the first landmark 2 years after MI for both PDC-groups (PDC&amp;gt;80%: 8.34%, 95% confidence interval [CI]: 8.04-8.63% and PDC≤80%: 10.75%, 95% CI: 9.80-11.69%) (Figure 2). The standardized relative risk of the composite endpoint was significantly higher for patients with PDC≤80% at all landmarks. A trend towards a diminished protective effect of long-term aspirin therapy appeared from 4 years after the index MI and onwards, decreasing from 1.40 (95% CI: 1.26-1.53) at second landmark 4 years after MI to 1.20 (95% CI: 1.04-1.35) at fourth landmark 8 years after MI. Overall, we found no difference in the relative risk of non-CV death between PDC-groups. Conclusion Suboptimal adherence to long-term aspirin therapy following MI was associated with an increased risk of recurrent MI, ischemic stroke, or death, but the relative risk appeared to decrease slightly over time from 4 years after the index MI and onwards.Figure 1Figure 2

Relation of Testosterone Normalization to Mortality and Myocardial Infarction in Men With Previous Myocardial Infarction

Background Coronary plaque burden and composition drive recurrent ischaemic events in coronary artery disease. Purpose We first investigated the association between plasma proteins and coronary plaque characteristics in a cohort of asymptomatic individuals with low-intermediate Framingham Risk Score. Plaque-related proteins were further evaluated in a second cohort of patients with acute coronary syndrome (ACS) to determine their prognostic value for predicting future myocardial infarction (MI). Methods We profiled 1305 plasma proteins using an aptamer-based array (SOMAscan) in asymptomatic individuals who had undergone 384-slice coronary computed tomography angiography. Plaques were categorized by composition as calcified or non-calcified. First, we identified proteins that were different (based on multiple testing adjusted p-values: q-value &lt;0.05) between 250 ACS patients who suffered a recurrent MI event on follow-up compared with another 250 ACS patients who remained event-free using Mann-Whitney U test. Next, protein candidates that also correlated (Pearson's p&lt;0.05) with specific categories of plaque composition were evaluated using a cox proportional hazards model to determine the risk of recurrent MI, adjusting for potential confounders in the second cohort. Results A total of 65 and 120 plasma proteins were significantly associated with calcified and non-calcified plaques respectively in the asymptomatic cohort (N=79). Of these 185 proteins, 23 proteins were differentially expressed (DE) between ACS patients with and without recurrent MI events (median follow-up 1811 days). The top three up-and down-regulated proteins in the recurrent MI group were macrophage-capping protein, trefoil factor 3 and cystatin-SN (median FC 1.22, 1.17 and 1.17; q-value 4.34x10–6, 2.18x10–4, 3.17x10–3 respectively) and fibroblast growth factor 20, lymphotoxin a2/b1 and vascular endothelial growth factor receptor 2 (median FC 0.92, 0.94 and −0.090; q-value 1.31x10–3, 9.45x10–3 and 3.90x10–3) respectively. The quartiles of these protein concentrations were also associated with risk of recurrent MI, (log-rank test p-value range from 2.71x10–7 to 0.04). Of the DE proteins, the adjusted hazards ratio (HR) of cystatin-SN in the highest quartile (Q4) was 1.44 times that of the first quartile (Q1) (adjusted HR: 1.44, 95% CI: 0.93–2.2) and higher plasma concentration of cystatin-SN was associated with increasing risk of recurrent MI events (Trend test p=0.004). On the other hand, the highest quartile of fibroblast growth factor 20 was associated with 44% reduction in risks of recurrent MI adjusted HR: 0.56, 95% CI of HR: 0.35–0.87), with significant trend test (p=0.0096). Conclusions Large-scale plasma proteomics identified novel plaque-related proteins predictive of recurrent coronary events in patients with ACS. Further studies may help unravel the biological underpinnings of these circulating proteins and their potential as novel prognostic biomarkers. Acknowledgement/Funding This work was supported by grant NMRC/CSA-INV/0001/2016 from the National Medical Research Council, Singapore.

Background There is a positive continuous association between Lipoprotein(a) (Lp[a]) levels and the risk of recurrent ischemic events in patients with recent myocardial infarction (MI). However, the prognostic significance of the association between high Lp(a) levels and diabetes has been poorly investigated after MI. Purpose The aim of this study was to evaluate the association of Lp(a) levels with the long-term risk of adverse events in post-MI patients, and to investigate whether diabetes may influence this association. Methods Consecutive MI patients who underwent urgent/emergent coronary angiography at our Institution from February 2013 to June 2019 were prospectively collected. Lp(a) serum concentrations was expressed for increasing range values (≤10, &amp;gt;10–30, &amp;gt;30–50, &amp;gt;50–70, and ≥70 mg/dL). The primary outcome was the recurrence of MI; the secondary outcome was all-cause death. The propensity score weighting technique was used to account for potential confounding between patients with and without diabetes. Results The study population consisted of 1018 post-MI patients (median age: 63 years; 76% males). Diabetes was reported in 280 patients (27.5%). The median value of Lp(a) was 10 mg/dL, and patients with diabetes showed significantly lower Lp(a) levels than patients without diabetes (p=0.025). At a median follow-up of 1121 days, the primary outcome was reported in 109 patients (10.7%), and the secondary outcome in 100 (9.8%). After propensity score weighting, there was a significant association between increasing Lp(a) range values and the primary outcome both in the overall population (p trend = 0.030) and in non-diabetic patients (p trend = 0.009), but not in diabetics. Conversely, no significant association with the risk of all-cause mortality across increasing Lp(a) categories both in the overall population and in the study groups according to the presence or not of diabetes was found. Compared with the lowest Lp(a) category, Lp(a) plasma levels &amp;gt;70 mg/dL were independently associated with the risk of recurrent MI (HR: 3.222; 95% CI, 1.225–8.478, p=0.018) and all-cause death (HR: 2.656; 95% CI, 1.009–6.991, p=0.048) in non-diabetic patients, but not in diabetics. Conclusions In this real-world post-MI population, Lp(a) serum levels were lower in diabetic than in non-diabetic patients. Increasing Lp(a) levels were significantly associated with the risk of recurrent MI, and very high Lp(a) serum concentration (&amp;gt;70 mg/dL) independently predicted recurrent MI and death in non-diabetic patients, but not in diabetics. These results reinforce the importance of routine assessment of Lp(a) levels after MI, particularly in patients without diabetes. Funding Acknowledgement Type of funding sources: None.

To investigate the association between long-term β-blocker therapy and clinical outcomes in patients without heart failure (HF) after acute myocardial infarction (AMI). Between 2010 and 2015, a total of 28970 patients who underwent coronary revascularization for AMI with β-blocker prescription at hospital discharge and were event-free from death, recurrent myocardial infarction (MI), or HF for 1 year were enrolled from Korean nationwide medical insurance data. The primary outcome was all-cause death. The secondary outcomes were recurrent MI, hospitalization for new HF, and a composite of all-cause death, recurrent MI, or hospitalization for new HF. Outcomes were compared between β-blocker therapy for ≥1 year (N = 22707) and β-blocker therapy for <1 year (N = 6263) using landmark analysis at 1 year after index MI. Compared with patients receiving β-blocker therapy for <1 year, those receiving β-blocker therapy for ≥1 year had significantly lower risks of all-cause death [adjusted hazard ratio (HR) 0.81; 95% confidence interval (CI) 0.72-0.91] and composite of all-cause death, recurrent MI, or hospitalization for new HF (adjusted HR 0.82; 95% CI 0.75-0.89), but not the risks of recurrent MI or hospitalization for new HF. The lower risk of all-cause death associated with persistent β-blocker therapy was observed beyond 2 years (adjusted HR 0.86; 95% CI 0.75-0.99) but not beyond 3 years (adjusted HR 0.87; 95% CI 0.73-1.03) after MI. In this nationwide cohort, β-blocker therapy for ≥1 year after MI was associated with reduced all-cause death among patients with AMI without HF.

BackgroundThe role of beta-blockers in acute myocardial infarction patients without heart failure and with preserved left ventricular ejection fraction (LVEF ≥ 50%) is unknown. Our study aimed to retrospectively analyze the associations of beta-blockers on such patients.MethodsThis is a multicenter, retrospective study. After screening 5,332 acute myocardial infarction patients, a total of 2519 patients without heart failure and with LVEF ≥ 50% were included. The patients were divided into two groups: the prescribed (n = 2049) and unprescribed (n = 470) beta-blockers group. The propensity score inverse probability treatment weighting was used to control confounding factors. We analyzed the associations between beta-blockers and outcomes in the short-term (1-year) and long-term (median, 3.61 years).ResultsThe primary outcome was all-cause mortality. The secondary outcomes were all-cause rehospitalization, cardiac death, recurrent myocardial infarction, new-onset heart failure rehospitalization. This study shows no statistically significant association between discharged with beta-blockers and all-cause mortality, either in the short-term [IPTW Adjusted, HR 1.02; 95%CI 0.43–2.40; P = 0.966] or long-term [IPTW Adjusted, HR 1.17; 95%CI 0.70–1.94; P = 0.547]. Discharged with beta-blockers was significantly associated with a reduced risk of short-term recurrent myocardial infarction [IPTW Adjusted, HR 0.44; 95%CI 0.20–0.97; P = 0.043], but there was no long-term relationship [IPTW Adjusted, HR 1.11; 95%CI 0.61–2.03; P = 0.735]. Other outcomes, such as new-onset heart failure rehospitalization and all-cause rehospitalization, were not observed with meaningful differences in either the short- or long-term. The results of sensitivity analysis were consistent with this.ConclusionsBeta-blockers might be associated with a reduced risk of recurrent myocardial infarction in patients without heart failure and with preserved left ventricular ejection fraction after acute myocardial infarction, in the short term. Beta-blockers might not be related to all-cause mortality in those patients, either in the short-term or long-term.Clinical trial registration Influence of Beta-blockers on Prognosis in Patients with Acute Myocardial Infarction Complicated with Normal Ejection Fraction, NCT04485988, Registered on 24/07/2020. Retrospectively registered.