Prognostic impact of peripheral artery disease in patients with and without high bleeding risk undergoing percutaneous coronary intervention.

BACKGROUND: Peripheral artery disease (PAD) is associated with worse outcomes after percutaneous coronary intervention (PCI). The aim of this study was to assess the prognostic impact of PAD according to high bleeding risk (HBR) status. METHODS: Consecutive patients undergoing PCI with drug-eluting stent implantation at a tertiary-care center (Mount Sinai Hospital) between 2012 and 2019 were stratified according to HBR and PAD status. The primary outcome was major adverse cardiac events (MACE), a composite of all-cause death, myocardial infarction (MI), and stroke 1 year after PCI. Secondary outcomes included major bleeding. RESULTS: Out of 16,750 patients, 43% were HBR and 57% were no-HBR. Within the two groups, PAD patients were 14% and 6%, respectively, and were more likely to have comorbidities and to undergo complex PCI than no-PAD patients. Within the HBR group, PAD was associated with an increased risk of MACE (11.4% vs. 7.3%, hazard ratio [HR]: 1.59, 95% confidence interval [CI]: 1.27-1.99, p < 0.001) and a numerical nonsignificant increase of major bleeding (8.5% vs. 6.9%, HR: 1.25, 95% CI: 0.98-1.59, p = 0.066) as compared with no-PAD. Among no-HBR patients, rates of MACE and major bleeding were numerically but not significantly higher in the PAD group. After multivariable adjustment, PAD was no longer a predictor of adverse outcomes, irrespective of HBR status. CONCLUSIONS: At 1-year after PCI, PAD was associated with increased 1-year risks of MACE in HBR patients. After adjustment for cardiovascular risk factors and comorbidities, the effect of PAD on adverse events was largely attenuated.

Long-Term Efficacy of Evolocumab in Patients With or Without Multivessel Coronary Disease.

BACKGROUND: In FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk), during a median follow-up of 2.2 years, risk reduction for major adverse cardiovascular event with evolocumab was greater in patients with multivessel disease (MVD). The FOURIER Open-Label Extension (FOURIER-OLE) provides an additional median follow-up of 5 years. OBJECTIVES: The purpose of this study was to assess the long-term benefit of evolocumab in patients with and without MVD. METHODS: FOURIER randomized 27,564 patients to evolocumab vs placebo; 6,635 entered FOURIER-OLE. Patients with coronary artery disease were categorized based on the presence of MVD (≥40% stenosis in ≥2 large vessels). The primary endpoint was cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization; the key secondary endpoint was cardiovascular death, myocardial infarction, or stroke. RESULTS: Of 23,656 patients in FOURIER with coronary artery disease, 25.4% had MVD; 5,887 patients continued into FOURIER-OLE. The risk reduction with initial allocation to evolocumab tended to be greater in patients with MVD than in those without: 23% (HR: 0.77 [95% CI: 0.68-0.87]) vs 11% (HR: 0.89 [95% CI: 0.82-0.96]) for the primary and 31% (HR: 0.69 [95% CI: 0.59-0.81]) vs 15% (HR: 0.85 [95% CI: 0.77-0.94]) for the key secondary endpoints (Pinteraction = 0.062 and Pinteraction = 0.031, respectively). The magnitude of benefit tended to grow during the first several years, reaching 37% to 38% reductions in risk in patients with MVD and 23% to 28% reductions in risk in patients without MVD. CONCLUSIONS: Evolocumab reduced the rate of major adverse cardiovascular event in patients with and without MVD. The benefit tended to occur earlier and was larger in patients with MVD. However, the magnitude grew over time in both groups. These data support early initiation of intensive low-density lipoprotein cholesterol lowering both in patients with and without MVD.

Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

Association between long-term exposure to ambient air pollution and lesion ischemia in patients with atherosclerosis.

BACKGROUND AND AIMS: Air pollution has been associated with coronary artery disease. The underlying mechanisms were understudied, especially in relation to coronary stenosis leading to myocardial ischemia. Advances in computed tomography (CT) allow for novel quantification of lesion ischemia. We aim to investigate associations between air pollution exposures and fractional flow reserve on CT (CT-FFR), a measure of coronary artery blood flow. METHODS: CT-FFR, which defines a ratio of maximal myocardial blood flow compared to its normal value (range: 0-100%), was characterized in 2017 patients with atherosclerosis between 2015 and 2017. Exposures to ozone (O3), nitrogen dioxide (NO2), and fine particulate matter (PM2.5) were estimated using high-resolution exposure models. Linear and logistic regression models were used to assess the association of each air pollutant with CT-FFR and with the prevalence of clinically relevant myocardial ischemia (CT-FFR <75%). RESULTS: Participants were on average 60.1 years old. Annual mean O3, NO2, PM2.5 were 61, 47 and 60 µg/m3, respectively. Mean CT-FFR value was 76.9%. In the main analysis, a higher level of O3 was associated with a lower CT-FFR value (-1.74%, 95% CI: -2.85, -0.63 per 8 µg/m3) and a higher prevalence of myocardial ischemia (odds ratio: 1.32, 95% CI: 1.05-1.65), adjusting for potential confounders such as risk factors and plaque phenotypes, independent of the effects of exposure to NO2 and PM2.5. No associations were observed for PM2.5 or NO2 with CT-FFR. CONCLUSIONS: Long-term exposure to O3 is associated with lower CT-FFR value in atherosclerotic patients, indicating higher risk of lesion ischemia.

Coronary Inflammation by Computed Tomography Pericoronary Fat Attenuation and Increased Cytokines in Young Male Anabolic Androgenic Steroid Users. / Inflamação Coronária Avaliada pela Atenuação de Gordura Pericoronária na Tomografia Computadorizada e Elevação de Citocinas em Usuários Jovens de Esteroides Anabólicos Androgênicos.

BACKGROUND: Anabolic androgenic steroid (AAS) abuse has been associated with coronary artery disease (CAD). Pericoronary fat attenuation (pFA) is a marker of coronary inflammation, which is key in the atherosclerotic process. OBJECTIVE: To evaluate pFA and inflammatory profile in AAS users. METHODS: Twenty strength-trained AAS users (AASU), 20 AAS nonusers (AASNU), and 10 sedentary controls (SC) were evaluated. Coronary inflammation was evaluated by mean pericoronary fat attenuation (mPFA) in the right coronary artery (RCA), left anterior descending coronary artery (LAD), and left circumflex (LCx). Interleukin (IL)-1 (IL-1), IL-6, IL-10, and TNF-alpha were evaluated by optical density (OD) in a spectrophotometer with a 450 nm filter. P<0.05 indicated statistical significance. RESULTS: AASU had higher mPFA in the RCA (-65.87 [70.51-60.70] vs. -78.07 [83.66-72.87] vs.-78.46 [85.41-71.99] Hounsfield Units (HU), respectively, p<0.001) and mPFA in the LAD (-71.47 [76.40-66.61] vs. -79.32 [84.37-74.59] vs. -82.52 [88.44-75.81] HU, respectively, p=0.006) compared with AASNU and SC. mPFA in the LCx was not different between AASU, AASNU, and SC (-72.41 [77.17-70.37] vs. -80.13 [86.22-72.23] vs. -78.29 [80.63-72.29] HU, respectively, p=0.163). AASU compared with AASNU and SC, had higher IL-1, (0.975 [0.847-1.250] vs. 0.437 [0.311-0.565] vs. 0.530 [0.402-0.780] OD, respectively, p=0.002), IL-6 (1.195 [0.947-1.405] vs. 0.427 [0.377-0.577] vs. 0.605 [0.332-0.950] OD, p=0.005) and IL-10 (1.145 [0.920-1.292] vs. 0.477 [0.382-0.591] vs. 0.340 [0.316-0.560] OD, p<0.001). TNF-α was not different between the AASU, AASNU, and SC groups (0.520 [0.250-0.610] vs. 0.377 [0.261-0.548] vs. 0.350 [0.182-430]), respectively. CONCLUSION: Compared with ASSNU and controls, AASU have higher mPFA and higher systemic inflammatory cytokines profile suggesting that AAS may induce coronary atherosclerosis through coronary and systemic inflammation.

FUNDAMENTO: O uso abusivo de esteroides anabólicos androgênicos (EAA) tem sido associado à doença arterial coronariana (DAC). A atenuação de gordura pericoronária (AGp) é um marcador de inflamação coronária, a qual exerce um papel chave no processo aterosclerótico. OBJETIVO: Avaliar AGp e perfil inflamatório em usuários de EAA. MÉTODO: Vinte indivíduos que realizavam treinamento de força, usuários de EAA (UEAA), 20 não usuários de EAA (NUEAA), e 10 indivíduos sedentários controle (SC) foram avaliados. Inflamação coronária foi avaliada por atenuação de gordura pericoronária média (AGPm) artéria coronária direita (ACD), artéria descendente anterior esquerda (ADA) e artéria circunflexa (ACX). Interleucina (IL)-1 (IL-1), IL-6, IL-10, e TNF-alfa foram avaliados por densidade ótica (DO) em um espectrofotômetro com um filtro de 450 nm. Um p<0,05 indicou significância estatística. RESULTADOS: Os UEAA apresentaram maior AGPm na ACD [-65,87 (70,51-60,70) vs. -78,07 (83,66-72,87) vs.-78,46 (85,41-71,99] unidades Hounsfield (HU), respectivamente, p<0,001) e AGPm na ADA [-71,47 (76,40-66,610 vs. -79,32 (84,37-74,59) vs. -82,52 (88,44-75,81) HU, respectivamente, p=0,006) em comparação aos NUEAA e CS. A AGPm na ACX não foi diferente entre os grupos UEAA, NUEAA e CS [-72,41 (77,17-70,37) vs. -80,13 (86,22-72,23) vs. -78,29 (80,63-72,29) HU, respectivamente, p=0,163). Em comparação aos NUEAA e aos CS, o grupo UEAA apresentaram maiores níveis de IL-1 [0,975 (0,847-1,250) vs. 0,437 (0,311-0,565) vs. 0,530 (0,402-0,780) DO, respectivamente, p=0,002), IL-6 [1,195 (0,947-1,405) vs. 0,427 (0,377-0,577) vs. 0,605 (0,332-0,950) DO, p=0,005) e IL-10 [1,145 (0,920-1,292) vs. 0,477 (0,382-0,591) vs. 0,340 (0,316-0,560) DO, p<0,001]. TNF-α não foi diferente entre os grupos UEAA, NUEAA e CS [0,520 (0,250-0,610) vs. 0,377 (0.261-0,548) vs. 0,350 (0,182-430)]. CONCLUSÃO: Em comparação aos NUEAA e controles, os UEAA apresentam maior AGPm e maior perfil de citocinas inflamatórias sistêmicas, sugerindo que os EAA podem induzir aterosclerose por inflamação coronária e sistêmica.

Contrast media volume reduction with the DyeVertTM system to prevent acute kidney injury in stable patients undergoing coronary procedures.

BACKGROUND: Contrast associated acute kidney injury (CA-AKI) can lead to an increased risk of adverse events. Contrast media (CM) volume reduction has been advocated as a pivotal strategy to prevent CA-AKI in stable patients undergoing percutaneous coronary procedures. AIMS: To compare the effectiveness of CM volume reduction with the DyeVertTM system versus conventional strategy in reducing the risk of CA-AKI. METHODS: We prospectively collected data from 136 patients with stable coronary artery disease at high risk of CA-AKI treated with left ventricular end diastolic pressure (LVEDP)- guided hydration and undergoing interventions with the use of the DyeVertTM (Osprey Medical Inc.) system. Patients previously enrolled in the LVEDP-guided hydration arm of the "Renal Insufficiency Following Contrast MEDIA Administration triaL III" (REMEDIAL III) were considered as controls. Propensity score was used to perform 1:1 matching to adjust for major confounders. The primary outcome was the occurrence of CA-AKI, as defined by an absolute increase of creatinine values ≥0.3 mg/dL at 48 h. RESULTS: Patients in the DyeVert group were treated with a significant lower CM volume (median: 47.5 vs. 84.0 mL, p < 0.001). The trend in creatinine increase was lower (p = 0.004) and the Δ of creatinine (0-48 h) showed a higher drop (-0.18 vs. -0.10 mg/dL, p = 0.036) in the DyeVert group. The risk of CA-AKI was significantly lower in DyeVert group compared to control group (5.1% vs. 16.8%; odds ratio 0.27, 95% confidence interval [0.12-0.61]). CONCLUSIONS: CM volume reduction with the DyeVertTM system seems to be superior to conventional strategies in reducing the occurrence of CA-AKI.

P2Y12 Inhibitor or Aspirin Monotherapy for Secondary Prevention of Coronary Events.

BACKGROUND: Aspirin is the only antiplatelet agent with a Class I recommendation for long-term prevention of cardiovascular events in patients with coronary artery disease (CAD). There is inconsistent evidence on how it compares with alternative antiplatelet agents. OBJECTIVES: This study compared P2Y12 inhibitor monotherapy vs aspirin in patients with CAD. METHODS: We conducted a patient-level meta-analysis of randomized trials comparing P2Y12 inhibitor monotherapy vs aspirin monotherapy for the prevention of cardiovascular events in patients with established CAD. The primary outcome was the composite of cardiovascular death, myocardial infarction, and stroke. Prespecified key secondary outcomes were major bleeding and net adverse clinical events (the composite of the primary outcome and major bleeding). Data were pooled in a 1-step meta-analysis. RESULTS: Patient-level data were obtained from 7 trials. Overall, 24,325 participants were available for analysis, including 12,178 patients assigned to receive P2Y12 inhibitor monotherapy (clopidogrel in 7,545 [62.0%], ticagrelor in 4,633 [38.0%]) and 12,147 assigned to receive aspirin. Risk of the primary outcome was lower with P2Y12 inhibitor monotherapy compared with aspirin over 2 years (HR: 0.88; 95% CI: 0.79-0.97; P = 0.012), mainly owing to less myocardial infarction (HR: 0.77; 95% CI: 0.66-0.90; P < 0.001). Major bleeding was similar (HR: 0.87; 95% CI: 0.70-1.09; P = 0.23) and net adverse clinical events were lower (HR: 0.89; 95% CI: 0.81-0.98; P = 0.020) with P2Y12 inhibitors. The treatment effect was consistent across prespecified subgroups and types of P2Y12 inhibitors. CONCLUSIONS: Given its superior efficacy and similar overall safety, P2Y12 inhibitor monotherapy might be preferred over aspirin monotherapy for long-term secondary prevention in patients with established CAD. (P2Y12 Inhibitor or Aspirin Monotherapy as Secondary Prevention in Patients With Coronary Artery Disease: An Individual Patient Data Meta-Analysis of Randomized Trials [PANTHER collaborative initiative]; CRD42021290774).

Association study of urinary iodine concentrations and coronary artery disease among adults in the USA: National Health and Nutrition Examination Survey 2003-2018.

Iodine is a vital trace element in the human body and is associated with several important coronary artery disease (CAD) risk factors. We aimed to explore the correlation between urinary iodine concentration (UIC) and CAD. Data from 15 793 US adults in the National Health and Nutrition Examination Survey (2003-2018) were analysed. We conducted multivariable logistic regression models and fitted smoothing curves to study the correlation between UIC and CAD. Furthermore, we performed subgroup analysis to investigate possible effect modifiers between them. We found a J-shaped association between UIC and CAD, with an inflection point at Lg UIC = 2·65 µg/l. This result indicated a neutral association (OR 0·89; 95 % CI 0·68, 1·16) between UIC and CAD as Lg UIC < 2·65 µg/l, but the per natural Lg [UIC] increment was OR 2·29; 95 % CI 1·53, 3·43 as Lg UIC ≥ 2·65 µg/l. An interaction between diabetes and UIC might exist. The increase in UIC results in an increase in CAD prevalence (OR 1·84, 95 % CI 1·32, 2·58) in diabetes but results in little to no difference in non-diabetes (OR 0·98, 95 % CI 0·77, 1·25). The J-shaped correlation between UIC and CAD and the interaction between diabetes and UIC should be confirmed in a prospective study with a series of UIC measurements. If excessive iodine precedes CAD, then this new finding could guide clinical practice and prevent iodine deficiency from being overcorrected.

Impact of pre-burn statin use on metabolic and cardiovascular disorders.

INTRODUCTION: Statins are among the most widely prescribed medications with proven effectiveness in patients with hyperlipidemia and atherosclerotic cardiovascular diseases. We investigated the relationship between statin use, metabolic and cardiovascular outcomes after burn. METHODS: We utilized data from the TriNetX electronic health database. Burn patients with prior statin use were compared to patients without prior use and analyzed the occurrence of metabolic and cardiovascular disorders. RESULTS: Prior statin use burn patients were 1.33 times as likely to develop hyperglycemia, 1.20 times for cardiac arrhythmia, 1.70 times for coronary artery disease (CAD), 1.10 times for sepsis, and 0.80 times for death. High percent TBSA burn, male sex, and lipophilic statin use were associated with higher odds of outcome development. CONCLUSION: Prior statin use in severely burned patients is associated with an increased risk of developing hyperglycemia, arrhythmias, and CAD, with higher odds in males, higher TBSA burn, and lipophilic statin users.

Review of Case Reports on Adverse Events Related to Pre-workout Supplements Containing Synephrine.

The use of pre-workout supplements has become increasingly popular, including the use of supplements containing synephrine. Synephrine might stimulate weight loss and improve sports performance by its proposed adrenergic properties. However, with its increasing popularity, numerous cases of adverse events related to synephrine use have been reported. This study provides a comprehensive overview and analysis of current case reports related to the supplemental use of synephrine. The scientific literature on cases of adverse events related to synephrine intake was collected through August 2021 using Pubmed and Google Scholar and subsequently reviewed and analysed. We obtained 30 case reports describing a total of 35 patients who suffered from medical complaints following use of synephrine-containing supplements. The patients most often presented with chest pain, palpitations, syncope and dizziness. Commonly raised diagnoses were ischaemic heart disease, cardiac arrhythmias and cerebrovascular disease. Five patients were left disabled or remained on medication at last follow-up. We here show an association between the use of pre-workout supplements containing synephrine and adverse events, mainly related to the cardiovascular system. However, we cannot exclude a role of possible confounding factors such as caffeine. Thus, the use of pre-workout supplements containing synephrine may lead to serious adverse health events, and therefore, caution is needed.

Long-term follow-up of contemporary drug-eluting stent implantation in diabetic patients: Subanalysis of a randomized controlled trial.

OBJECTIVE: The elevated risk of adverse events following percutaneous coronary intervention in diabetic patients persists with newer-generation DES. The polymer-free amphilimus-eluting stent (PF-AES) possesses characteristics with a potentially enhanced performance in patients with diabetes. Data from the 1-year follow-up period has been previously published. The aim of this subanalysis was to assess long-term performance of two contemporary drug-eluting stents (DES) in a diabetic population. METHODS: In the ReCre8 trial, patients were stratified for diabetes and troponin status, and randomized to implantation of a permanent polymer zotarolimus-eluting stent (PP-ZES) or PF-AES. The primary endpoint was target-lesion failure (TLF), a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. Clinical outcomes between discharge and 3 years follow-up were assessed. RESULTS: A total of 302 patients with diabetes were included in this analysis. After 3 years, TLF occurred in 12.5% of PP-ZES patients versus 10.0% in PF-AES patients (p = 0.46). Similarly, the separate components of TLF were comparable between the two study arms. The secondary composite endpoint of NACE was higher in the PP-ZES arm with 45 cases (29.6%) versus 30 cases (20.0%) in the PF-AES arm (p = 0.036). In the insulin-dependent diabetic population, TLF occurred in 19.1% of PP-ZES patients versus 10.4% of PF-AES patients (p = 0.21). NACE occurred in 40.4% of PP-ZES patients versus 27.1% of PF-AES patients (p = 0.10). CONCLUSIONS: This subanalysis shows that the use of PF-AES results in similar clinical outcomes as compared to PP-ZES, yet some benefits of use of PF-AES in diabetic patients may prevail. Future dedicated trials should confirm these findings.

Are air quality perception and PM2.5 exposure differently associated with cardiovascular and respiratory disease mortality in Brussels? Findings from a census-based study.

BACKGROUND: There is ample evidence that air pollution increases mortality risk, but most studies are based on modelled estimates of air pollution, while the subjective perception of air quality is scarcely assessed. We aimed to compare the effects of objective and subjective exposure to air pollution on cardiorespiratory mortality in Brussels, Belgium. METHODS: Data consisted of the 2001 Belgian census linked to registry-based mortality data for the follow-up period 2001-2014. We included individuals aged >30 years of age residing in Brussels at baseline (2001). Air pollution exposure was assessed with objective (modelled annual mean concentrations of PM2.5 in micrograms per cubic metre, µg/m3) and subjective indicators (poor self-reported air quality perception in the census). We used Cox Proportional Hazard models with age as the underlying time scale to evaluate associations with cardiovascular disease (CVD) and respiratory disease mortality, and separately, ischaemic heart disease (IHD), cerebrovascular disease, and COPD excluding asthma mortality. We specified single- and two-exposure models and evaluated effect modification by neighbourhood unemployment rate. RESULTS: 437,340 individuals were included at baseline. During follow-up (2001-2014), 22,821 (5%) individuals had died from CVDs and 8572 (2%) from respiratory diseases. In single-exposure models, PM2.5 was significantly associated with an increased risk in CVD and IHD mortality (e.g. for IHD, per 5 µg/m3 increase: Hazard Ratio, HR:1.22, 95%CI:1.08-1.37), and poor air quality perception with COPD excluding asthma mortality (HR:1.23, 95%CI:1.15-1.33). Associations remained significant in the two-exposure models, and additionally, perception was associated with respiratory disease mortality. Associations became gradually stronger with increasing neighbourhood unemployment rate [e.g. in the highest, Q3: PM2.5 and cerebrovascular disease mortality (HR:1.53, 95%CI:1.04-2.24)]. CONCLUSION: Our findings suggest that objective and subjective exposure to air pollution increased the risk of dying from cardiovascular and respiratory diseases respectively in Brussels. These results encourage policies reducing pollution load in Brussels whilst considering socio-economic inequalities.

Eligibility and Implementation of Rivaroxaban for Secondary Prevention of Atherothrombosis in Clinical Practice-Insights From the CANHEART Study.

Background The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) trial decreased major adverse cardiovascular events with very low-dose rivaroxaban and aspirin in patients with coronary artery disease and peripheral artery disease. We examined the eligibility and potential real-world impact of this strategy on the COMPASS-eligible population. Methods and Results COMPASS eligibility criteria were applied to the CANHEART (Cardiovascular Health in Ambulatory Care Research Team) registry, a population-based cohort of Ontario adults. We compared 5-year major adverse cardiovascular events and major bleeding rates stratified by COMPASS eligibility and by clinical risk factors. We applied COMPASS trial rivaroxaban/aspirin arm hazard ratios to estimate the potential impact on the COMPASS-eligible cohort. Among 362 797 patients with coronary artery disease or peripheral artery disease, 38% were deemed eligible, 47% ineligible, and 15% indeterminate. Among eligible patients, a greater number of risk factors was associated with higher rates of cardiovascular outcomes, whereas bleeding rates increased minimally. Over 5 years, applying COMPASS treatment effects to eligible patients resulted in a 2.4% absolute risk reduction of major adverse cardiovascular events and a number needed to treat of 42, and a 1.3% absolute risk increase of major bleeding and number needed to harm (NNH) of 77. Those with at least 2 risk factors had a 3.0% absolute risk reduction of major adverse cardiovascular events (number needed to treat =34) and a 1.6% absolute risk increase of major bleeding (number needed to harm =61). Conclusions Implementation of very-low-dose rivaroxaban therapy would potentially impact ≈$$ \approx $$2 in 5 patients with atherosclerotic disease in Ontario. Eligible individuals with ≥$$ \ge $$2 comorbidities represent a high-risk subgroup that may derive the greatest benefit-to-risk ratio. Selection of patients with high-risk predisposing factors appears appropriate in routine practice.

Biomarker Prediction of Complex Coronary Revascularization Procedures in the FOURIER Trial.

BACKGROUND: Biomarkers are known to predict major adverse cardiovascular events. However, the association of biomarkers with complex coronary revascularization procedures or high-risk coronary anatomy at the time of revascularization is not understood. OBJECTIVES: We examined the associations between baseline biomarkers and major coronary events (MCE) and complex revascularization procedures. METHODS: FOURIER was a randomized trial of the proprotein convertase subtilisin-kexin type 9 inhibitor evolocumab vs placebo in 27,564 patients with stable atherosclerosis. We analyzed adjusted associations among the biomarkers, MCE (coronary death, myocardial infarction, or revascularization), and complex revascularization (coronary artery bypass graft or complex percutaneous coronary intervention) using a multimarker score with 1 point assigned for each elevated biomarker (high-sensitivity C-reactive protein ≥2 mg/L; N-terminal pro-B-type natriuretic peptide ≥450 pg/mL; high-sensitivity troponin I ≥6 ng/L; growth-differentiation factor-15 ≥1,800 pg/mL). RESULTS: When patients were grouped by the number of elevated biomarkers (0 biomarkers, n = 6,444; 1-2 biomarkers, n = 12,439; ≥3 biomarkers, n = 2,761), there was a significant graded association between biomarker score and the risk of MCE (intermediate score: HRadj: 1.57 [95% CI: 1.38-1.78]; high score: HRadj: 2.90 [95% CI: 2.47-3.40]), and for complex revascularization (intermediate: HRadj: 1.33 [95% CI: 1.06-1.67]; high score: HRadj: 2.07 [95% CI: 1.52-2.83]) and its components (Ptrend <0.05 for each). The number of elevated biomarkers also correlated with the presence of left main disease, multivessel disease, or chronic total occlusion at the time of revascularization (P < 0.05 for each). CONCLUSIONS: A biomarker-based strategy identifies stable patients at risk for coronary events, including coronary artery bypass graft surgery and complex percutaneous coronary intervention, and predicts high-risk coronary anatomy at the time of revascularization. These findings provide insight into the relationships between cardiovascular biomarkers, coronary anatomical complexity, and incident clinical events. (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk [FOURIER]; NCT01764633).

Unravelling the role of macrophages in cardiovascular inflammation through imaging: a state-of-the-art review.

Cardiovascular disease remains the leading cause of death and disability for patients across the world. Our understanding of atherosclerosis as a primary cholesterol issue has diversified, with a significant dysregulated inflammatory component that largely remains untreated and continues to drive persistent cardiovascular risk. Macrophages are central to atherosclerotic inflammation, and they exist along a functional spectrum between pro-inflammatory and anti-inflammatory extremes. Recent clinical trials have demonstrated a reduction in major cardiovascular events with some, but not all, anti-inflammatory therapies. The recent addition of colchicine to societal guidelines for the prevention of recurrent cardiovascular events in high-risk patients with chronic coronary syndromes highlights the real-world utility of this class of therapies. A highly targeted approach to modification of interleukin-1-dependent pathways shows promise with several novel agents in development, although excessive immunosuppression and resulting serious infection have proven a barrier to implementation into clinical practice. Current risk stratification tools to identify high-risk patients for secondary prevention are either inadequately robust or prohibitively expensive and invasive. A non-invasive and relatively inexpensive method to identify patients who will benefit most from novel anti-inflammatory therapies is required, a role likely to be fulfilled by functional imaging methods. This review article outlines our current understanding of the inflammatory biology of atherosclerosis, upcoming therapies and recent landmark clinical trials, imaging modalities (both invasive and non-invasive) and the current landscape surrounding functional imaging including through targeted nuclear and nanobody tracer development and their application.

Trends in the Prevalence and Incidence of Opium Abuse and its Association with Coronary Artery Risk Factors in Adult Population in Iran: Findings from Kerman Coronary Artery Disease Risk Factors Study.

Background: The prevalence of opium addiction in Iran is high probably due to the belief that opium has preventive effects against cardiovascular diseases. In the second phase of Kerman coronary artery disease risk factors study, the prevalence, incidence rate, and the association between opium use and other coronary artery disease risk factors (CADRFs) were assessed. Methods: In a cross-sectional study (2014-2018), 9996 inhabitants of Kerman, southeastern Iran, aged 15-80 years were recruited to the study. After taking fasting blood samples, the participants were examined or interviewed for demographic data and CADRFs, including opium use. The participants were categorized into "never", "occasional", and "dependent" users. The association between opium use and CADRFs was assessed with adjusted regression analysis (Stata v.11 software). Results: The overall prevalence of opium consumption was lower than that of five years earlier (P<0.01). The prevalence was currently higher in men than women and decreased in men between the two phases (P<0.001). There was a positive correlation between opium use and depression (P<0.001), anxiety (P<0.05), and a negative association with the level of physical activity (P<0.001). The five-year incident rate of dependent and occasional opium use was 4.2 and 3.9 persons/100 person-years, respectively. The incidence of opium use was higher in diabetic, hypertensive, depressed, anxious, and obese subjects. Conclusion: The study did not demonstrate any protective effects of opium on CADRFs. Considering the higher rate of opium use in subjects with hypertension, diabetes, obesity, and psychological disorders, the health authorities should implement educational programs to warn and correct the unsafe belief.

Positive Effect of Air Purifier Intervention on Baroreflex Sensitivity and Biomarkers of Oxidative Stress in Patients with Coronary Artery Disease: A Randomized Crossover Intervention Trial.

Exposure to fine particulate matter increases the risk of cardiovascular morbidity and mortality. Few studies have tested the beneficial effect of indoor air filtration intervention in patients with cardiovascular disease. The aim of this study is to investigate the effect of air filtration on mitigating cardiovascular health in patients with coronary artery disease. This randomized, double-blind, crossover study is conducted with 38 coronary artery disease patients. The intervention consists of the following three periods: two-week active and sham air filtration interventions, with a two-week washout period. The indoor PM2.5 concentration is continuously monitored during the entire study period. We measure the blood pressure, heart rate variability, baroreflex sensitivity, autonomic function test results, and endothelial function. The two-week active air filtration intervention for two weeks reduces the average indoor concentration of PM2.5 by 33.9%. The indoor PM2.5 concentration is significantly correlated to cross-correlation baroreflex sensitivity. Active air filtration is significantly associated with a decrease in the indicator of oxidative stress represented as 8-hydroxy-2'-deoxyguanosine. This study shows that a short-term air filtration intervention improved baroreflex sensitivity and might reduce oxidative stress in coronary artery disease patients. These findings suggest that the use of an air purifier could mitigate the recurrence of cardiovascular disease events in patients with coronary artery disease.

Analysis of Thromboembolic and Thrombocytopenic Events After the AZD1222, BNT162b2, and MRNA-1273 COVID-19 Vaccines in 3 Nordic Countries.

Importance: Vaccinations are paramount to halt the COVID-19 pandemic, and safety data are essential to determine the risk-benefit ratio of each COVID-19 vaccine. Objective: To evaluate the association between the AZD1222, BNT162b2, and mRNA-1273 vaccines and subsequent thromboembolic and thrombocytopenic events. Design, Setting, and Participants: This self-controlled case series used individual-level data from national registries in Norway, Finland, and Denmark. Participants included individuals with hospital contacts because of coronary artery disease, coagulation disorders, or cerebrovascular disease between January 1, 2020, and May 16, 2021. Exposures: AZD1222, BNT162b2, or mRNA-1273 vaccine. Main Outcomes and Measure: Relative rate (RR) of hospital contacts for coronary artery disease, coagulation disorders, or cerebrovascular disease in a 28-day period following vaccination compared with the control period prior to vaccination. Results: We found 265 339 hospital contacts, of whom 112 984 [43%] were for female patients, 246 092 [93%] were for patients born in 1971 or earlier, 116 931 [44%] were for coronary artery disease, 55 445 [21%] were for coagulation disorders, and 92 963 [35%] were for cerebrovascular disease. In the 28-day period following vaccination, there was an increased rate of coronary artery disease following mRNA-1273 vaccination (RR, 1.13 [95% CI, 1.02-1.25]), but not following AZD1222 vaccination (RR, 0.92 [95% CI, 0.82-1.03]) or BNT162b2 vaccination (RR, 0.96 [95% CI, 0.92-0.99]). There was an observed increased rate of coagulation disorders following all 3 vaccines (AZD1222: RR, 2.01 [95% CI, 1.75-2.31]; BNT162b2: RR, 1.12 [95% CI, 1.07-1.19]; and mRNA-1273: RR, 1.26 [95% CI, 1.07-1.47]). There was also an observed increased rate of cerebrovascular disease following all 3 vaccines (AZD1222: RR, 1.32 [95% CI, 1.16-1.52]; BNT162b2: RR, 1.09 [95% CI, 1.05-1.13]; and mRNA-1273: RR, 1.21 [95% CI, 1.09-1.35]). For individual diseases within the main outcomes, 2 notably high rates were observed: 12.04 (95% CI, 5.37-26.99) for cerebral venous thrombosis and 4.29 (95% CI, 2.96-6.20) for thrombocytopenia, corresponding to 1.6 (95% CI, 0.6-2.6) and 4.9 (95% CI, 2.9-6.9) excess events per 100 000 doses, respectively, following AZD1222 vaccination. Conclusions and Relevance: In this self-controlled case series, there was an increased rate of hospital contacts because of coagulation disorders and cerebrovascular disease, especially for thrombocytopenia and cerebral venous thrombosis, following vaccination with AZD1222. Although increased rates of several thromboembolic and thrombocytopenic outcomes following BNT162b2 and mRNA-1273 vaccination were observed, these increases were less than the rates observed after AZD1222, and sensitivity analyses were not consistent. Confirmatory analysis on the 2 mRNA vaccines by other methods are warranted.

Benefit and risk of prolonged dual antiplatelet therapy after drug-eluting stent implantation in patients with chronic kidney disease: A nationwide cohort study.

BACKGROUND AND AIMS: The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) with drug-eluting stent in patients with chronic kidney disease (CKD) is not clearly established. This study purposed to compare clinical outcomes of patients with 6-12 (standard) versus 12-24 months (prolonged) DAPT according to CKD. METHODS: Using a nationwide, claim-based database, we retrospectively evaluated association between DAPT duration and clinical outcomes including death, composite ischemic event, and composite bleeding event between 1 and 3 years after PCI. CKD was defined as estimated glomerular filtration rate <60 mL/min/1.73 m2. Of 73,941 eligible patients, 13,425 (18.2%) had CKD and 49,019 (66%) were prescribed prolonged DAPT. Prolonged DAPT had no significant impact on the risk of clinical outcomes in patients with normal renal function. RESULTS: In patients with CKD, prolonged DAPT was associated with a lower risk of all-cause death (HR 0.85, 95% CI 0.76-0.95) and composite ischemic events (HR 0.87, 95% CI 0.78-0.96) and a higher risk of composite bleeding events (HR 1.18, 95% CI 1.02-1.37). Benefit of prolonged DAPT on reducing composite ischemic event increased significantly in patients with worsened renal dysfunction (pinteraction = 0.02) while there was no significant interaction between its bleeding risk and renal dysfunction (pinteraction = 0.22). CONCLUSIONS: While standard DAPT would be recommended in patients with normal renal function, tailored decision for DAPT duration would be considered in those with CKD to balance between ischemic and bleeding risks.

Clinical outcomes after permanent polymer or polymer-free stent implantation in patients with diabetes mellitus: The ReCre8 diabetes substudy.

OBJECTIVES: The purpose of this analysis was to compare target-lesion failure (TLF) of a permanent polymer zotarolimus-eluting stent (PP-ZES) versus a polymer-free amphilimus-eluting stent (PF-AES) in diabetics. BACKGROUND: The improvement of outcomes with new-generation drug-eluting stent as seen in the general population is less pronounced among diabetics. The PF-AES introduces an elution-technology with potential enhanced performance in diabetics. METHODS: In this subanalysis of the ReCre8 trial, patients were randomized to either a PP-ZES or PF-AES after stratification for diabetes and troponin status. The primary device-oriented endpoint was TLF, a composite of cardiac death, target-vessel myocardial infarction and target-lesion revascularization. RESULTS: In the ReCre8 trial, 304 (20%) patients were diabetic and 96 (6%) had insulin-dependent diabetes mellitus. There was no statistically significant difference between the two study arms regarding the primary endpoint (PP-ZES 7.2% vs. PF-AES 4.0%; p = .21), although the composite of net adverse clinical events was higher in the PP-ZES arm (15.7 vs. 8.0%; p = .035). Stent thrombosis was low in both groups with no cases in the PP-ZES arm and 1 case in the PF-AES arm (p = .32). Regarding insulin-treated diabetics, TLF was higher in the PP-ZES arm (14.9 vs. 2.1%; p = .022). CONCLUSIONS: Diabetics could potentially benefit from a dedicated stent, releasing sirolimus with a lipophilic carrier (amphilimus-formulation). Future trials should confirm the potential benefit of a PF-AES in this population.