Cardiovascular Risk Research Articles

Ankle brachial index,a non invasive tool predicts cardiovascular events after acute myocardial infarction:a 3 year follow -up study

Abstract Background / Introduction The ankle-brachial index (ABI) is a non-invasive tool that was initially used for the diagnosis of lower-extremity peripheral artery disease (PAD). It has been proven that ABI is a marker of atherosclerosis in other vascular sites and can therefore be used to predict cardiovascular events regardless the presence or not of PAD symptoms. Purpose This study aims to examine the prognostic value of ABI in the setting of acute myocardial infarction (MI), as up till now there is not enough relevant evidence. Method We followed up 441 patients [79% male;mean age 62 years;67% hypertnesive; 30% with diabetes mellitus (DM); 52% current smokers] who were hospitalized because of MI for a period of three years. All patients underwent baseline estimation of clinical and laboratory parameters during theri hospitalization.The ABI was measured according to established methodology using a certified automated device and abnormal ABI defined as a value ≤ 0.9. The primary endpoint was a composite of all-cause and cardiovascular death, as well as major cardiovascular events including decompensated heart failure, new acute coronary syndrome, cerebrovascular event, malignant arrhythmia, PAD event and new onset renal dysfunction. All events were assessed both in-hospital and within 3 years of follow-up. Results Our study population had a mean ABI of 1.1 (IQR: 1.00 to 1.18). With the use of reduced multivariate regression models ABI was proven to be a prognostic indicator for the in-hospital composite endpoint. Patients with an abnormal ABI had a threefold risk of in-hospital events [HR 2.93, 95% CI: 1.48-5.81, p=0.002]. After conducting multivariate analysis ABI maintained its predictive power of all-cause mortality [HR 2.88, 95% CI: 1.53 – 5.42, p=0.001], regardless of hypertension DM, LDL levels and smoking status of the study population in 3 years follow-up. Conclusion An impaired ABI is associated with greater risk of in-hospital events in patients with acute MI. Moreover, ABI emerges as an independent predictor of long-term all-cause mortality in those patients.The findings of this study suggest that subclinical and clinical PAD are associated with poor outcomes among patients with acute MI; thus, routine ABI tests enhance risk stratification and might carry important prognostic significance in these patients regardless of PAD symptoms.

Spinal cord injury and risk of overall and type specific cardiovascular diseases: A meta-analysis.

Cardiovascular disease (CVD) is a growing concern among people with spinal cord injury (SCI). This meta-analysis aims to explore the risk of overall CVD and specific types of cardiovascular events among SCI patients. This meta-analysis is registered on PROSPERO (CRD CRD42024537888). The data sources comprised PubMed, Embase, the Cochrane Library, and reference lists of the included studies. The literature collection span is from database establishment until April 17, 2024. This meta-analysis encompassed observational studies investigating the association between SCI and the risk of overall types of CVD or specific CVD types. Risk of bias was evaluated utilizing the Newcastle-Ottawa Quality Assessment Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ) Scale. Odds ratios (ORs) with 95% confidence intervals (CIs) were aggregated using a random-effects model. Our initial search generated 5357 relevant records form these international databases. This meta-analysis encompassed 9 observational studies involving 2,282,691 individuals, comprising 193,045 patients with SCI and 2,209,646 controls. We observed a 1.56-fold [OR = 1.56, 95% CI (1.43, 1.70), I2 = 91.3%, P < 0.001] rise in the risk of overall types of CVD among SCI patients, with a 1.82-fold increase in males and a 1.76-fold increase in females. SCI patients without comorbidities exhibited a 2.10-fold elevated risk of overall CVD types, while those with comorbidities had a 1.48-fold increased risk. Concerning specific CVD types, SCI patients showed a 1.58-fold [OR = 1.57, 95% CI (1.22, 2.03), I2 = 92.4%] higher risk of myocardial infarction, a 1.52-fold [OR = 1.52, 95% CI (1.07, 2.16), I2 = 88.7%] increase in atrial fibrillation, a 1.64-fold [OR = 1.64, 95% CI (1.22, 2.20), I2 = 95.5%] elevation in heart failure risk, and 2.38-fold [OR = 2.38, 95% CI (1.29, 4.40), I2 = 92.5%] increments in stroke risk. But there was no statistically significant difference in the risk of hypertension [OR = 1.54, 95% CI (0.98, 2.42), I2 = 96.6%]. The risk of overall CVD in SCI patients surpassed that of the non-SCI control group, with elevated risks of specific cardiovascular events like myocardial infarction, atrial fibrillation, heart failure, and stroke. Clinicians should prioritize awareness of CVD risks in SCI patients.

Relation of apolipoprotein C3 to risk of major adverse cardiovascular events and death after acute coronary syndrome on a background of optimized statin treatment

Abstract Background Apolipoprotein C3 (ApoC3), a component of triglyceride-rich lipoproteins and some low-density lipoprotein and high-density lipoprotein particles, has been shown to predict incident coronary heart disease (CHD) and major adverse cardiovascular events (MACE). However, it is unknown whether ApoC3 predicts risk in patients with acute coronary syndrome (ACS) receiving contemporary therapies including optimized statin treatment, and if any such association is independent of apolipoprotein B (ApoB) levels. Purpose We assessed the association of ApoC3 with first MACE (CHD death, nonfatal myocardial infarction, fatal or nonfatal ischaemic stroke, or hospitalization for unstable angina) and all-cause death in patients with recent ACS treated with high-intensity or maximum-tolerated statin and blinded PCSK9 inhibitor (alirocumab, ALI) or placebo (PBO). Methods ApoC3 was measured by mass spectrometry at baseline (n=11,956) and after 4 months (M4; n=11,176) of treatment with ALI or PBO in the ODYSSEY OUTCOMES trial (which had 18,924 total participants). In continuous and spline analyses adjusted for treatment group and ApoB, we assessed the association of baseline ApoC3 with risk of MACE and death. In the ALI group we determined association of change in ApoC3 from baseline to M4 with risk of MACE and death after M4 in a model adjusted for baseline ApoC3 and ApoB, and the change in ApoB from baseline to M4. Results Median (Q1, Q3) baseline ApoC3 concentration was in a normal range [85 (65, 113) mg/L]. Continuous ApoC3 was not related to MACE (p=0.50) or death (p=0.51); spline analysis showed a slight curvilinear association of baseline ApoC3 with risk of MACE and death, but no clinically meaningful relationship (Figure). Findings were similar in the PBO group alone, and without adjustment for ApoB (data not shown). At M4, the median (Q1, Q3) change from baseline in ApoC3 was -10 (-27, -5; p&amp;lt;0.0001) mg/L with ALI and 2 (-14, 18; P = NS) mg/L with PBO. Overall, ALI significantly reduced the incidence of MACE (10.1% vs 12.1%; p=0.0006) and death (3.5% vs 4.2%; p=0.045) compared with PBO among those with available baseline ApoC3. However, the change in ApoC3 on treatment with ALI did not predict the risk of MACE or death after M4. Findings were qualitatively similar without adjustment for ApoB or its change. Conclusion In a cohort with recent ACS receiving optimized statin therapy and with median baseline ApoC3 in a normal range, ApoC3 did not provide clinically meaningful prediction of cardiovascular events or death. A modest reduction of ApoC3 by ALI did not associate with subsequent risk of MACE or death. It remains uncertain whether targeted therapies producing larger reductions in ApoC3 from higher baseline levels will affect cardiovascular risk.

Type 2 diabetes individuals have a shorter QRS duration, prolonged QTc interval, flatter T wave, and reduced left ventricular cycle volumes compared to matched controls in the UK Biobank

Abstract Background Type 2 diabetes is associated with an increased risk of heart failure even in the absence of overt coronary artery disease, though underlying mechanisms are unclear. ECG and cardiac magnetic resonance (CMR) imaging provide windows into subclinical changes in myocardial structure and function and could be exploited to understand this. Purpose We investigate differences in ECG and CMR biomarkers in a large cohort of participants with type 2 diabetes, compared to a matched control cohort. We hypothesise that individuals with diabetes may exhibit concurrent differences in biomarkers, reflecting underlying cardiac remodelling. Methods We carried out a pair-matched cross-sectional study to examine the association between type 2 diabetes and multi-modal cardiac biomarkers. The exposure cohort consists of 1,781 UK Biobank participants with an imaging and ECG visit, prevalent type 2 diabetes and no known cardiovascular events at the time of visit. The control cohort is matched on age, sex and body mass index (BMI), and consists of 1,781 participants without diabetes. ECG and CMR biomarkers derived from UK Biobank data were used as outcome variables. We built four multiple multivariate linear regression models, incrementally adjusted for socio-demographic, lifestyle, and clinical covariates. Results Both cohorts were mostly male (63.6%), had a median age of 67 years [IQR: 72-85] and a median BMI of 27.8 kg/m2 [24.6-31.0]. Individuals with type 2 diabetes were more likely to be non-white (7.9% vs 2.7%, p&amp;lt;0.001), current or previous smokers (43.6% vs 40.6%, p=0.04), have lower diastolic blood pressure (79 [72-85] vs 81 [74-88] mmHg, p&amp;lt;0.001), and take cholesterol medication (72.3% vs 27.2%, p&amp;lt;0.001); anti-hypertensives (56.3% vs 27.3%, p&amp;lt;0.001); insulin (13.7% vs 0.1%, p&amp;lt;0.001); and metformin (53.1% vs 0.1%, p&amp;lt;0.001). They had a higher ventricular rate, shorter QRS duration, longer QTc interval, and flatter T wave amplitude, as well as lower left ventricular end-diastolic and end-systolic volumes, among other differences (Table 1). Covariates including cholesterol medication, metformin, and HbA1c were excluded as they were strongly correlated with diabetes, age and/or sex (Pearson correlation coefficient &amp;gt;0.3 or &amp;lt;-0.3). After full adjustment, we found that the exposure variable, diabetes, had a statistically significant association with ventricular rate, QRS duration, T wave offset, T wave amplitude in lead V3, left ventricular stroke volume and global average thickness (p&amp;lt;0.05) (Table 2). Conclusion Our results reveal that individuals with type 2 diabetes exhibit a shorter QRS, longer QTc, and lower end-diastolic and end-systolic volumes, compared to matched controls. This may be indicative of subclinical cardiac abnormalities, both electrophysiological and mechanical. Our association analysis suggests that other factors correlated with diabetes may be also responsible for certain biomarker differences and their underlying causes.

Comparative outcomes between empagliflozin and dapagliflozin in heart failure: real world multi-center cohort study

Abstract Introduction Heart failure (HF) is a significant global health concern, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, such as dapagliflozin and empagliflozin, have emerged as important therapeutic options. However, their comparative effectiveness in a real-world population remains uncertain. Purpose The purpose of this multicenter, population-based cohort study was to investigate and compare the outcomes associated with dapagliflozin and empagliflozin use in patients with heart failure. We sought to understand whether these SGLT2 inhibitors had differential effects on cardiovascular events in a real-world setting. Methods We analysed data from a clinical data warehouse encompassing seven medical centers. Subjects diagnosed with heart failure between January 2021 and November 2023, who were prescribed dapagliflozin or empagliflozin, were included. We conducted one-to-one propensity-score matching, ensuring that the dapagliflozin and empagliflozin groups were comparable in baseline characteristics. The primary outcome was a composite of cardiovascular (CV) death or hospitalization for HF, analysed as the first event occurring after starting each medication. Secondary outcomes included individual components, all-cause death, and CV hospitalization. Results Propensity-score matching made a balanced cohort of 6,281 patients (3,111 in the dapagliflozin group and 3,170 in the empagliflozin group). The median follow-up duration was 16.0 months. In the propensity-score matched cohort, dapagliflozin and empagliflozin showed no significant difference in the primary outcome (8.8% versus 7.8%, hazard ratio [HR] 0.91, 95% confidence interval [CI] 0.77-1.08, p=0.276). Similar findings were observed in secondary outcomes. Subgroup analysis revealed potential benefits of empagliflozin in patients with diabetes mellitus (DM) (7.8% versus 5.6%, HR 0.73, 95% CI 0.55-0.98, p=0.039). Conclusion This study suggests that dapagliflozin and empagliflozin have similar clinical outcomes in the management of heart failure in a real-world setting. However, empagliflozin showed result in improving outcomes for HF patients with DM. Further research is warranted to validate these findings and guide clinical decision-making in the individualized management of heart failure.Baseline characteristicsSubgroup analysis

Body mass index may alter cardiovascular outcomes in patients with newly-diagnosed atrial fibrillation and previous stroke: an interaction analysis using longitudinal data from the GLORIA-AF registry

Abstract Background Patients with new onset atrial fibrillation (AF) and previous stroke (PS) are at higher risk of cardiovascular (CV) outcomes. An obesity paradox, where overweight or obese patients have better outcomes, has been seen. Whether body mass index (BMI) modify the risks of cardiovascular (CV) events and mortality in AF patients with PS remains uncertain. Purpose To ascertain whether BMI of AF patients with PS events alters risks of CV outcomes. Methods A cohort from phase III of the prospective GLORIA-AF (Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients With Atrial Fibrillation) was included. Risks of Major Adverse Cardiovascular Events (MACE), CV death, and all-cause mortality were analysed using COX proportional hazard regression with interaction terms added between PS and the BMI characteristics. Results Data from 17482 patients [median age: 71.0 (IQR: 64.0–78.0) years; 45.3% female] with newly-diagnosed AF were analysed and included in risk models. At baseline, 1840 (10.5%) patients with AF had PS in which 1694 (9.7%) and 170 (0.97%) patients had one (1 PS) and ≥2 (2 PS) respectively. After a median follow-up of 3.0 (IQR: 2.9–3.1) years, 1111 MACE, 562 CV deaths, and 1266 all-cause deaths were recorded. In a multivariate COX regression model, interaction between BMI and PS was significant in predicting risk of CV death (Pint =0.019). BMI was also associated with increased risk of CV death among AF patients with ≥1 PS. The interaction between PS and BMI was borderline significant in predicting MACE (Pint=0.063) and all-cause death (Pint=0.057). Figure 1 showed the different risks associated with different BMI statuses. Conclusion The risks of adverse CV outcomes were higher in AF patients with higher BMI and previous stroke. An obesity paradox was not evident in AF patients with previous stroke.Figure 1

Is the obesity paradox leading to a less stringent secondary prevention strategy in post-acute coronary syndrome patients?

Abstract Introduction Patients with acute coronary syndrome (ACS) are at very high risk of recurrent cardiovascular (CV) events. Despite being a major CV risk factor, obesity was associated with best survival in patients with ACS, the so-called "obesity paradox". It is uncertain if this finding is leading to a less stringent secondary prevention strategy in this group of patients, and whether it influences prognosis. Purpose To analyze the impact of obesity on outcomes after ACS and on other CV risk factor management. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 cardiac rehabilitation (CR) program in 2017, with a follow-up of 24 months. Patients were classified in 2 groups according to body mass index (BMI) at baseline: Group 1 (G1) were obese patients (BMI≥30 kg/m2), and Group 2 (G2) were non-obese patients (BMI&amp;lt;30kg/m2). Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results 198 patients were included (mean age of 60.3±10.7 years, 82% male) with a mean BMI of 27.7±4.2 kg/m2. Forty-seven patients (23.7%) had a BMI≥30 kg/m2. Patients in G1 were more likely to have hypertension (79% vs 55%; p=0.003) and diabetes (36% vs 20%; p=0.022). CR program was associated with smoking cessation, significant BMI (G1: -0.69 (95%CI: -0.40 to -0.10); G2: -0.39 (95%CI: -0.20 to -0.57) and LDL-Cholesterol (LDL-C) reduction (G1: -38 (95%CI: -25 to -50); G2: -29 (95%CI: -22 to -36), and functional capacity improvement (G1: +1.2 METs (95%CI: +0.9 to +1.5); G2: +1.1 METs (95%CI: +1.0 to +1.4) in both groups at 3 months, with similar magnitude of improvement. At 24 months, BMI had returned to baseline values in both groups, while the improvement in smoking status, LDL-C and functional capacity persisted. At 24 months, MACE occurrence was numerically increased in obese group (G1: 26.1% vs. G2: 17.2%, p=0.182), with a statistically significant higher incidence of non-fatal recurrent ACS in G1 (17% vs. 7.3%, p=0.048). Conclusions ACS patients with obesity have worse prognosis, despite the similar improvement in CV risk profile. Our data also suggests that, despite the short-term improvement in BMI, current treatment strategies are not effective at achieving a persistent weight control over 24-months.

Residual cardiovascular risk in patients with acute coronary syndromes: from hs-CRP and LDL-C to JCAD

Abstract Background Patients with a recent acute coronary syndrome (ACS) remain at high residual cardiovascular risk to which cholesterol, inflammation, and yet-to-be-identified pathways jointly contribute (1). The novel Junctional Protein Associated with Coronary Artery Disease (JCAD) protein drives incident cardiovascular events via pathways, among them fibrinolysis, that act independently from lipid metabolism and inflammation (2). Purpose Whether circulating JCAD provides predictive utility over and above established risk factors among ACS patients at residual lipid risk (RLR), residual inflammatory risk (RIR), or both (RILR), remains unknown. Methods Among patients participating in the multicentre SPUM-ACS study, patients at RLR (on-statin LDL-C ≥70.0 mg/dl), RIR (on-statin hs-CRP ≥2.0 mg/l) or both (RILR; on-statin LDL-C ≥70.0 mg/dl and CRP ≥2.0 mg/l),(1,3) and propensity-score matched (PSM) controls were identified, and the contributions of plasma hs-CRP, LDL-C and JCAD toward recurrent major adverse cardiovascular events (MACE; defined as a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke) were studied by fitting uni- and multivariable-adjusted Cox proportional hazard regression models. Results Patients at RLR, RIR, or both (RILR) were at higher MACE risk compared to controls (hazard ratio [HR] per log2 increase, 1.51; 95% confidence interval (CI), 1.05-2.17; HR, 1.78; 95% CI, 1.23-2.58; and HR 1.75; 95% CI, 1.12-2.74; Figure 1). Among those at RLR, MACE risk increased with increasing levels of hs-CRP and JCAD, respectively, in uni- (HR, 1.17; 95% CI, 1.06–1.30; HR, 1.29; 95% CI, 1.03-1.62) and multivariable-adjusted models (adjusted [a]HR, 1.16; 95% CI, 1.03–1.30; aHR, 1.27; 95% CI, 1.01-1.60), whereas no association of LDL-C and future MACE risk was noted. Similarly, among patients at RIR, MACE risk increased by 1.28-fold per log2 increase in plasma JCAD (HR, 1.28; 95% CI, 1.03–1.59), which prevailed in multivariable-adjusted models accounting for potential confounders (aHR, 1.31; 95% CI, 1.04–1.65). In ACS patients at both residual inflammatory and lipid risk, MACE risk associated almost linearly with increasing JCAD levels (HR, 1.45; 95% CI, 1.09–1.92), independently of potential confounders (aHR, 1.47; 95% CI, 1.11–1.97). Meanwhile, no association of LDL-C or hs-CRP with MACE risk was identified among these high-risk patients (Figure 2). Conclusions ACS patients at RIR, RLR, or both are at high ischaemic risk, with JCAD ranking among the top predictors of MACE across the broad spectrum of residual risk. Our data highlight the importance of novel pathways to address residual cardiovascular risk, with JCAD ranking among most promising candidates.

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 &amp;lt;$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.

Standard modifiable risk factors (SMuRF) paradox for the prognosis in the patients with acute myocardial infarction

Abstract Background Hypertension, diabetes, dyslipidemia and smoking are recognized as standard modifiable risk factors (SMuRFs) for adverse cardiovascular events such as acute myocardial infarction (AMI). Recent studies have shown that AMI patients without SMuRFs are associated with increased mortality compared to those with SMuRFs. However, the relationship between the number of SMuRFs in patients with AMI and mortality has not been well evaluated. Purpose The purpose of this study was to evaluate the clinical characteristics and prognosis of AMI patients stratified by the number of SMuRFs. Methods We studied 6,706 AMI patients between 2013 and 2021 using data from the Mie ACS registry, a retrospective and multicenter registry. For the purpose of this study, only AMI patients as their first cardiovascular events were included in this analysis. Therefore, after excluding patients with a known history of coronary artery disease (n=982), 5724 AMI patients were included in the current analysis. All-cause mortality was compared with 30-day and after 30-day mortality in AMI patients stratified by the number of SMuRFs as the primary outcome. In addition, all-cause mortality rate was compared in AMI patients without and with SMuRFs after propensity score matching on age, sex, body mass index, Killip classification, cardiac arrest before presentation, multivessel disease, left main truck disease, hemoglobin and emergent percutaneous coronary intervention. Results Among 5,724 AMI patients, 672 patients (11.7%) did not have SMuRFs. The median age of patients without SMuRFs was higher than that of patients with any SMuRFs (73 y.o. vs. 70 y.o, P&amp;lt;0.001), and higher prevalence of female and severe Killip class was observed in patients without SMuRFs compared with those with any SMuRFs (P&amp;lt;0.001, respectively). According to the KM survival curves stratified by number of SMURFs, an increased number of SMURFs was associated with higher 30-day survival rates (P=0.035), and the 30-day landmark analysis showed a trend toward higher survival in patients with the highest number of SMURFs, although not statistically significant (Figure1). Multivariate Cox regression analysis showed that 0 SMuRF was an independent prognostic factor for 30-day mortality with hazard ratio of 1.55 (95%CI; 1.13-2.13, P&amp;lt;0.001). In addition, KM survival curves after propensity score matched analysis showed the poor 30-day mortality in 0 SMuRF group (P=0.036), there was no significant difference in after 30-day mortality between the two groups (Figure 2). Conclusions Patients without SMuRFs had a high 30-day mortality rate, but once they survived the acute phase, their prognosis was comparable to patients with SMuRFs. Moreover, the SMuRF paradox was recognized in the acute phase. This finding highlights the need for early identification of the individuals at risk of developing MI despite the absence of SMuRFs and strict acute management regardless of the number of SMuRFs.

Combination of moderate-intensity statins and ezetimibe versus high-intensity statins alone for primary prevention of cardiovascular events

Abstract Background Combination of a moderate-intensity statin with ezetimibe can lead to similar reductions in cardiovascular events as monotherapy with a high-intensity statin in patients with established atherosclerotic cardiovascular disease (ASCVD). The comparative effectiveness of these two cholesterol-lowering strategies in the primary prevention setting is unknown. Purpose To compare incident ASCVD events associated with a combination of moderate-intensity statin and ezetimibe versus monotherapy with a high-intensity statin in adults without prior history of cardiovascular disease. Methods We conducted a new-user active comparator retrospective population-based cohort study in Canada. We included all adults aged ≥ 67 years (eligible for drug coverage) with a first prescription of either a combination of moderate-intensity statin with ezetimibe ("combination therapy") or high-intensity statin alone between January 2010 and December 2022. Patients were excluded if they had not received any prior lipid lowering therapies or had a history of myocardial infarction (MI), stroke, heart failure, peripheral vascular disease or prior coronary revascularisation at any time before or within 3 months of treatment initiation. The primary outcome was a composite of all-cause death, hospitalization for MI or stroke, or coronary revascularization. An inverse probability of treatment weighting propensity score was used to account for confounding (demographics, comorbidities, laboratory tests, other medications). Results Among 67,884 patients (mean age: 74.0±5.5y; 53% females), 8,798 (13%) initiated combination therapy and 59,086 (87%) initiated a high-intensity statin. At 1 year, after weighting, the mean achieved LDL-C was ~1.9 mmol/L in both groups. The median follow-up was 6.5 years. The cumulative incidence of the primary outcome at 10 years in the weighted cohort was 32.7% in the combination therapy group and 36.1% in the high-intensity statin group (HR: 0.87; 95% CI: 0.82 to 0.92; p&amp;lt;0.001; absolute risk reduction: 3.5%; 95% CI: 0.8 to 6.1; Figure 1). This result was primarily driven by a lower risk of all-cause death (HR: 0.85; 95% CI: 0.80 to 0.91; p&amp;lt;0.001; Figure 2) and stroke (cause-specific [cs] HR: 0.86; 95% CI 0.74 to 0.99; p=0.04), whereas no differences were observed in the risk of MI (csHR: 0.97; 95% CI: 0.82 to 1.15) or coronary revascularization (csHR: 0.97; 95% CI 0.85 to 1.11). Conclusion The combination of moderate-intensity statins with ezetimibe was associated with a lower risk of incident ASCVD compared with high-intensity statins alone among primary prevention patients in a real-world setting. These results were driven by a lower risk of all-cause death and stroke, but not coronary events. The influence of statin intolerance on the allocated strategy and adherence to therapy cannot be addressed in this analysis, which, along with verifying these estimates, may be best determined in a prospective randomized trial.

The incidence of death and risk factors for mortality following major bleeding in patients anticoagulated with factor Xa inhibitors: an observational study in the UK clinical setting (AXIOM UK)

Abstract Background Major bleeding (MB) in association with anticoagulant use results in significant mortality. Mortality can be directly attributed to bleeding, or may follow bleeding complications such acute kidney injury, myocardial infarction, stroke and other cardiovascular events. Most real-world data relating to bleeding mortality is derived from cohorts receiving vitamin-K antagonists. We investigated all-cause mortality (ACM) after MB in a large cohort anticoagulated with Factor Xa inhibitors (FXai), e.g. direct oral anticoagulants (DOAC) rivaroxaban, apixaban and low-molecular-weight heparins (LMWH). Purpose To describe incidence rates of and risk factors for ACM following MB in patients receiving FXai. To investigate MB related ACM by bleeding site, treatment indication, treatment subgroups and individual and cumulative time periods. Methods Retrospective cohort analysis of new users of FXai, between 2012-2020, for therapeutic indications including atrial fibrillation (AF), venous thromboembolism, bioprosthetic cardiac valves or adult congenital heart disease was conducted. MB was defined by the International Society on Thrombosis and Haemostasis (ISTH) criteria. Incidence rates were reported per 100 person-years. Sub-distribution hazard ratios with 95% confidence intervals (95% CI) were estimated from Fine and Gray regression models accounting for competing risks. Results In 240,357 new users of FXai, 88% used an oral FXai. The most common FXai indication was AF (72%). There were 10,163 patients (4.2%) hospitalised for bleeding events during FXai use. Of these, 3,873 MB events (38%) fulfilled the ISTH definition of MB and 1312 died during 3,542 person years of follow-up (Table 1). ACM incidence rates varied by time, indication, bleeding subtype, and drug type. ACM occurred in 926 patients (23.9%) in the first month. Mortality rates were highest in the first month 607 (95% CI 568-647) per 100 person years, the rates then decreased over the year but remained elevated throughout the first year compared with subsequent years. Those receiving LMWH had higher ACM than those receiving a DOAC, but this was not significant in the adjusted risk factor analysis. Risk factors for ACM following bleeding included age ≥80, and a history of current smoking, myocardial infarction, congestive heart failure, peripheral artery disease, Stage 4 or 5 kidney disease, metastatic cancer, and intracranial haemorrhage. Age&amp;lt;60, bleeding following major trauma, and a history of anaemia were associated with lower risk of ACM (Table 2). Conclusions There is a significant incidence of ACM following MB among FXai users. The incidence rate of ACM in patients treated with FXai was highest in the first month after FXai initiation, declined during the first year and then plateaued. Multiple risk factors associated with ACM have been recognised and these could guide urgent therapies such as antidotes.

Cardiovascular events in patients treated with bempedoic acid vs. placebo: systematic review and meta-analysis

Abstract Aims Reduction of low-density lipoprotein cholesterol (LDL-C) decreases cardiovascular mortality and morbidity. Bempedoic acid represents a promising novel lipid modifying agent for patients who cannot reach guideline recommended LDL-C goals or statin-intolerant patients, but data on safety and cardiovascular outcomes are limited. We therefore aimed to systematically review randomized controlled trials investigating bempedoic acid versus placebo in patients with hyperlipidemia. Methods A systematic search on the databases PubMed, Web of Science, and Embase until 20 March 2023 was performed. All randomized trials comparing bempedoic acid (180 mg daily) with placebo in patients with an indication for lipid-lowering therapy were included. As primary endpoint we analysed three-point major adverse cardiovascular events (MACE) consisting of cardiovascular death, non-fatal myocardial infarction (MI) or non-fatal stroke. The analysis was carried out using the odds ratio as the outcome measure. Due to the expected heterogeneity across studies a random-effects model was fitted to the data. Results Out of 258 manuscripts, 10 manuscripts fulfilled the inclusion criteria. In total, these trials included 18,200 patients (9,765 on bempedoic acid, 8,435 on placebo). Bempedoic acid significantly reduced MACE compared to placebo (OR 0.84 [95% CI 0.76-0.96]; p&amp;lt;0.001; I2=0%). The endpoint reduction was driven by a lower rate of non-fatal MI, whereas bempedoic acid had no significant effect on stroke (OR 0.86 [95% CI 0.69-1.08]; p=0.20, I2=0%) and all-cause mortality (OR 1.19 [95% CI 0.73-1.93]; p=0.49; I2=18%). Conclusion Bempedoic acid reduced non-fatal MI in patients with hyperlipidemia, whereas it had no significant effect on stroke and all-cause mortality.Figure.Forest plot for three-point MACE

Outcomes of post-acute coronary syndrome patients enrolled in a phase 2 cardiac rehabilitation program

Abstract Introduction Cardiac rehabilitation (CR) is a class I recommendation in the management of patients with acute coronary syndrome (ACS), namely ST-elevation myocardial infarction (STEMI) and non-ST acute coronary syndrome (NST-ACS). Reported mortality and recurrent cardiovascular (CV) events are still unacceptably high in these patients. Purpose To assess CV outcomes of patients enrolled in a CR program and its association with ACS presentation. Methods Single-center, retrospective observational study that included all consecutive post-ACS patients enrolled in a phase 2 CR program in 2017, with a follow-up of 24 months. Group 1 were patients with STEMI; group 2 were patients with NST-ACS. Major adverse cardiovascular events (MACE) were defined as a composite of death, non-fatal ACS, non-fatal stroke, and unplanned revascularization. Results Of the 202 ACS patients who attended the CR program in 2017, 4 were excluded due to missing data. Of the 198 patients analyzed (age 60.3±10.7 years, 82% male), 101 patients had a STEMI and 97 NST-ACS. STEMI patients were significantly younger (57±9.5 vs. 63±10, p&amp;lt;0.001), with fewer CV risk factors (diabetes 16% vs. 32%, p=0.008; hypertension 51% vs. 72%, p=0.002; obesity 17% vs. 31%, p=0.020; dyslipidemia 54% vs. 77%, p&amp;lt;0.001), except for active smoking (53% vs. 29%, p=0.001), and were less likely to have previous history of coronary artery disease (9% vs. 31%, p&amp;lt;0.001). During the 3-month CR program, both groups achieved significant reduction in body mass index, LDL-Cholesterol, functional capacity, and smoking cessation rates. At 3-, 12-, and 24-months evaluation, both groups showed no differences in risk factor management, nor differences in lipid-lowering therapy, namely percentage of high-intensity statin and ezetimibe use. STEMI patients were treated more frequently with ticagrelor (86% vs. 67%, p=0.001) at baseline. MACE occurrence was significantly lower in STEMI patients (11% vs. 28%, p=0.003), driven mainly by recurrent ACS (4% vs. 15%, p=0.006). Conclusions In our study, NST-ACS patients had significantly higher CV disease burden and worse outcomes at 24-month follow-up. Despite the heightened CV risk in this group, secondary prevention treatment intensity was similar in both groups.

Association of the lipoprotein(a) gene (LPA) p.Ile4399Met variant with lipoprotein(a) level and cardiovascular events in patients following coronary artery bypass grafting under 65 years of age

Abstract Introduction Lipoprotein(a) (Lp[a]), a well-known risk factor for atherosclerotic cardiovascular disease, is largely determined by variation in the Lp(a) gene (LPA) locus encoding apolipoprotein(a). The LPA gene Ile4399Met (rs3798220) variant has been previously reported to have a strong association with the Lp(a) level in patients with coronary artery disease (CAD), however, its prevalence in the middle-age patients after coronary artery bypass grafting (CABG) has not been investigated. Purpose To assess the frequency of the LPA gene c.5673A&amp;gt;G variant (p.Ile4399Met; rs3798220) in Polish patients with CAD following CABG under 65 years of age and determined its association with laboratory and clinical variables. Materials and Methods We studied 215 patients with stable CAD, aged 59.5±4.9 years, who underwent primary and isolated CABG surgery (at age of 57.8±5.4 years), including 195 (90.8%) male. Clinical characteristics and analysis of the LPA c.5673A&amp;gt;G variant were performed. Results The genotype distribution was as follows: AA – 192 (89.3%), AG – 19 (8.8%), and GG – 4 (1.9%). The c.5673G allele carriers had higher Lp(a) level (106.5 [IQR 77.9-149.7] vs 10.4 [IQR 4.4-43.0] mg/dL, p&amp;lt;0.001) compared with non-carriers. Among the c.5673G allele carriers, Lp(a) correlated positively with pack-years of smoking (r=0.563, p=0.045) and fibrinogen (r=0.431, p=0.040), but not with low-density lipoprotein cholesterol (r=0.202, 0.368). There were no other genotype-associated differences with regard to demographic and clinical variable between carriers and non-carriers, including myocardial infarction (56.5% vs 47.9%, p=0.511), peripheral artery disease (21.7% vs 15.1%, p=0.377) and cerebrovascular events (13.0% vs 6.7%, p=0.389). Conclusions To our knowledge, this is the first report on the prevalence of LPA rs3798220 variant in patients with advanced CAD following CABG surgery under 65 years of age. We showed a relatively high (10.7%) percentage of c.5673G allele carriers who have ten times higher Lp(a) levels compared to the wild type, however, its impact on cardiovascular events requires further studies.

Troponin T as a risk marker for recurrent cardiovascular events in the post-discharge setting one month after acute coronary syndrome: a TRACER substudy

Abstract Background Troponin T (TnT) is a protein found in cardiac myocytes that is released during myocardial injury, such as myocardial infarction (MI). TnT levels rapidly rise during an MI, remain elevated for several days, and are a key criterion for diagnosing MI. Additionally, circulating TnT levels may offer prognostic information later, particularly during the rehabilitation phase after an acute coronary syndrome (ACS). Purpose To examine the relationship between circulating TnT at one month after hospitalisation for ACS and subsequent cardiovascular (CV) events. Methods The TRACER trial randomly assigned 12,944 patients diagnosed with non-ST-segment elevation ACS (NSTE-ACS) to receive either vorapaxar or placebo. Plasma samples were obtained after one month, and high-sensitivity (hs)-TnT was measured among 5,313 patients using the Elecsys electrochemiluminescence immunoassays. In this sub-study, the primary composite endpoint was the one-year risk of CV mortality, MI, or ischaemic stroke. Associations with outcomes were evaluated using Cox regression models, both unadjusted and adjusted for clinical baseline characteristics. Results The median concentration of hs-TnT was 11 ng/L one month after hospitalisation for ACS. Higher levels of hs-TnT at one month were associated with older age, coronary artery bypass surgery during the index ACS, male sex, a history of heart failure, renal disease, and diabetes mellitus. The composite outcome of CV mortality, MI, or ischaemic stroke occurred in 381 patients (incidence rate 5.4 per 100 person-years). Hs-TnT at one month after ACS was independently associated with the risk of the composite CV endpoint (relative hazard ratio with 95% confidence interval comparing the third vs. the first sample quartile: 2.40 [1.80 – 3.20]) (see Figure 2). Similarly, hs-TnT, when added to a model including established risk factors, increased the concordance index of the multivariable model from 0.711 to 0.740 (p&amp;lt;0.001). The results were consistent across the different components of the composite endpoint. Conclusions The level of hs-TnT provides useful information on the risk of future CV events in patients when measured one month after an ACS. This information might be useful for optimising secondary preventive treatment following an ACS.Figure.Hs-TnT and composite CV outcome

Efficacy of native T1 mapping for patients with non-ischemic cardiomyopathy and ventricular functional mitral regurgitation undergoing transcatheter edge-to-edge repair

Abstract Background The objectives of this study were to investigate the efficacy of LV myocardial damage assessment by native T1 mapping obtained with cardiac magnetic resonance (CMR) for symptomatic heart failure (HF) patients with non-ischemic cardiomyopathy (NICM) and ventricular functional mitral regurgitation (VFMR) undergoing transcatheter edge-to-edge repair (TEER). Methods We studied 40 symptomatic HF patients with NICM and VFMR undergoing TEER. LV myocardial damage was defined as the native T1 Z-score which was converted from native T1 value obtained with CMR before TEER. The primary endpoint was defined as first re-hospitalization for HF or cardiovascular death over a median follow-up period of 12 months after TEER. Results Multivariable Cox-proportional hazards analysis showed that a native T1 Z-score was the only independent parameter associated with cardiovascular events (hazard ratio: 3.40, 95% confidential interval: 1.51-7.67), and patients with native T1 Z-score &amp;lt; 2.41 experienced significantly fewer cardiovascular events than those with a native T1 Z-score ≥ 2.41 (log-rank P = 0.001). Moreover, such a low native T1 Z-score and more severe VFMR in an effective regurgitant orifice area (EROA) ≥ 0.30 cm2 was associated with fewer cardiovascular events than for a high native T1 Z-score of ≥ 2.41 and less severe VFMR of EROA &amp;lt; 0.30 cm2 (log-rank P = 0.002). Conclusion Assessment of baseline LV myocardial damage by means of native T1 Z-score obtained with CMR without the use of gadolinium-based contrast media is a valuable additional parameter for better management of symptomatic NICM patients with reduced LVEF and VFMR following TEER.

Prognostic value of diffuse high-risk plaque in patients with acute myocardial infarction: a three-vessel optical coherence tomography study

Abstract Background Existing evidence has identified that high-risk plaque (HRP) characterized by a thin-cap fibroatheroma and/or a minimal lumen area ≤ 3.5 mm² were indicative of future cardiovascular events. Diffuse coronary artery disease also contributes to the poor prognosis. Purpose The present study aims to assess the prognostic value of diffuse HRP in patients with acute myocardial infarction (AMI) by using three-vessel optical coherence tomography (OCT). Methods A total of 674 patients with AMI who underwent OCT examination of three major epicardial arteries between January 2017 and December 2018 were consecutively studied. Among 2843 nonculprit lesions detected by OCT, 1375 (48.4%) HRPs were identified and divided into diffuse HRP group (lesion length &amp;gt;20mm, n=443) and focal HRP group (lesion length ≤20mm, n=932). Patients were followed up for a median period of 5 years. Major adverse cardiovascular event (MACE) was defined as the composite of cardiac death, nonculprit lesion-related nonfatal myocardial infarction, and unplanned coronary revascularization. Results The average age of all enrolled patients is 56.7±11.4 years, with 74.9% of male. As compared with focal HRP group, diffuse HRP group had longer lesion length [25.8(23.0,30.8) mm vs. 13.2(9.8,16.1) mm, P&amp;lt;0.001], longer lipid length [18.6(12.3,24.9) mm vs. 7.0(4.5,10.5) mm, P&amp;lt;0.001], and thinner minimal fibrous cap thickness [73.3(53.3,106.7) μm vs. 93.3(60.0,130.0) μm, P&amp;lt;0.001], whereas mean lipid arc was comparable between the two groups. The prevalence of nonculprit plaque rupture (14.2% vs. 7.8%, P&amp;lt;0.001) was significantly higher in diffuse HRP group than that in the focal HRP group. Nonculprit lesions in diffuse HRP group had higher incidence of macrophage accumulation, microvessels, cholesterol crystals, calcification, and layered plaque phenotype than those in focal HRP group (all P&amp;lt;0.001). The incidence of nonculprit lesion-related MACE was 4.7% in diffuse HRP group and 1.7% in focal HRP group [HR: 3.155, 95% confidence interval: 1.579 to 6.301, P=0.002]. Conclusions In patients with AMI, diffuse HRP at nonculprit segment has higher levels of plaque vulnerability and is predictive of future adverse cardiovascular events. Further studies are warranted to investigate the individual treatment strategy of diffuse and focal HRP.Figure 1.Nonculprit plaque vulnerabilityFigure 2.MACE

Dual pathway inhibition in patients with atherosclerosis with and without heart failure: insights from the XATOA Registry

Abstract Introduction Patients with atherosclerotic cardiovascular disease (ASCVD) are at a high-risk of experiencing a major adverse cardiovascular event, with 1 in 10 individuals experiencing an event within four years (1). To address this risk of secondary cardiovascular events, there have been renewed efforts to enhance secondary prevention therapies through the application of guideline-directed medical therapy. One secondary prevention strategy is the use of dual pathway inhibition (DPI) therapy with aspirin and vascular-dose rivaroxaban (2.5mg twice daily), which simultaneously targets both the platelet activation and thrombin generation pathways. Patients with concomitant ASCVD and heart failure (HF) are a subgroup with a higher risk for ischemic events, but have not been adequately represented in recent clinical trials. Purpose To explore the risks and benefits of DPI therapy in a generalizable population of patients with concomitant ASCVD and HF. Methods The Xarelto plus Acetylsalicylic acid Treatment patterns and Outcomes in patients with Atherosclerosis (XATOA) registry is a prospective, multicentre registry of patients with either coronary artery or peripheral artery disease that were initiated on DPI (2). The primary endpoint was a composite of cardiovascular death, myocardial infarction or stroke and the safety outcome was major bleeding. Multivariable logistic regression was performed to assess the association of HF status and ejection fraction (EF) on the outcomes of interest. Results Of 5532 participants, 4022 (72.7%) had documentation of HF status. Of those 873 (21.5%) had a history of heart failure (EF &amp;gt;40% - 461; EF ≤40% - 181, EF unknown – 231). Over a median follow-up of 465 days (IQR – 372-576), the primary outcome occurred in 4.9% of participants with HF compared to 2.4% in those without HF (aHR 1.57 95% CI 1.02-2.41). The safety outcome was similar in patients with and without HF (0.9% versus 1.11%; aHR 0.7 95% CI 0.31-1.67). Among patients with HF, those with an EF of ≤40% demonstrated a non-significant trend towards higher rates of adverse events including MACE (8.8% versus 3.5%; aHR 1.38; 95% CI 0.59-3.22) compared to those with an EF of &amp;gt; 40%. Conclusion In a generalizable cohort of patients with atherosclerotic disease and HF, the use of DPI is associated with similar outcomes to those observed in recent randomised controlled clinical trials.Table 1 - Demographics by HF statusFigure 1 - MACE by HF status

Neutrophil-to-lymphocyte ratio can predict the clinical prognosis of patients with primary adosteronism

Abstract Background Excess aldosterone-mediated inflammatory response is thought to be a factor in the high risk of cardiovascular events in patients with primary aldosteronism (PA). Leucocyte related inflammatory parameters, especially NLR, were significantly independent of aldosterone (PAC) in PA patients. However, the impact of NLR on the long-term prognosis of PA patients is unclear. Objective To explore the predictive value of neutrophil-to-lymphocyte ratio (NLR) on the long-term prognosis of patients with primary aldosteronism (PA). Methods The data for this study were derived from the Tianjin Health and Medical Big Data Super platform, comprising a retrospective cohort of patients discharged from 72 hospitals in our city from 2010 to 2023. According to the inclusion and exclusion criteria, 570 patients were ultimately included in the statistical analysis. Each patient had laboratory measurements, including blood cell counts, taken after admission and before interventional treatment. The primary endpoint was major cardiovascular events (MACEs), defined as cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke. Results During a mean follow-up period of 5 years, 125（21.9%）MACEs were recorded. ROC curve analysis displayed that the best cut-off value of NLR for predicting MACEs was 4.87. The MACEs of the high NLR group at 1 year, 3 years, and 5 years were higher than those of the low NLR group（25.0% vs 9.4%，40.3% vs17.1% 和 40.3% vs 19.3%；P＜0.05).Kaplan-Meier survival curve analysis showed that the survival rate of the low NLR group was higher than that of the high NLR group (P&amp;lt;0.001). The results of multivariate Cox proportional hazards regression analysis showed that NLR was an independent risk factor affecting the prognosis of PA patients, and the difference was statistically significant (P&amp;lt;0.05). Conclusions Elevated NLR is associated with adverse prognosis in patients with PA. NLR can serve as a simple and practical indicator to evaluate the long-term prognosis of PA patients. These findings warrant external validation, preferably in a prospective design.