Coronary artery disease (CAD) is an important contributor to the cardiovascular burden in cancer survivors. This review identifies features that could help guide decisions about the benefit of screening to assess the risk or presence of subclinical CAD. Screening may be appropriate in selected survivors based on risk factors and inflammatory burden. In cancer survivors who have undergone genetic testing, polygenic risk scores and clonal hematopoiesis markers may become useful CAD risk prediction tools in the future. The type of cancer (especially breast, hematological, gastrointestinal, and genitourinary) and the nature of treatment (radiotherapy, platinum agents, fluorouracil, hormonal therapy, tyrosine kinase inhibitors, endothelial growth factor inhibitors, and immune checkpoint inhibitors) are also important in determining risk. Therapeutic implications of positive screening include lifestyle and atherosclerosis interventions, and in specific instances, revascularization may be indicated.

Proteasome inhibitors (PIs) are the backbone of combination treatments for patients with multiple myeloma and AL amyloidosis, while also indicated in Waldenström\'s macroglobulinemia and other malignancies. PIs act on proteasome peptidases, causing proteome instability due to accumulating aggregated, unfolded, and/or damaged polypeptides; sustained proteome instability then induces cell cycle arrest and/or apoptosis. Carfilzomib, an intravenous irreversible PI, exhibits a more severe cardiovascular toxicity profile as compared with the orally administered ixazomib or intravenous reversible PI such as bortezomib. Cardiovascular toxicity includes heart failure, hypertension, arrhythmias, and acute coronary syndromes. Because PIs are critical components of the treatment of hematological malignancies and amyloidosis, managing their cardiovascular toxicity involves identifying patients at risk, diagnosing toxicity early at the preclinical level, and offering cardioprotection if needed. Future research is required to elucidate underlying mechanisms, improve risk stratification, define the optimal management strategy, and develop new PIs with safe cardiovascular profiles.

UNASSIGNED: Patients with coronary artery disease and impaired renal function are at higher risk for both bleeding and ischemic adverse events after percutaneous coronary intervention (PCI).
UNASSIGNED: This study assessed the efficacy and safety of a prasugrel-based de-escalation strategy in patients with impaired renal function.
UNASSIGNED: We conducted a post hoc analysis of the HOST-REDUCE-POLYTECH-ACS study. Patients with available estimated glomerular filtration rate (eGFR) (n = 2,311) were categorized into 3 groups. (high eGFR: >90 mL/min; intermediate eGFR: 60 to 90 mL/min; and low eGFR: <60 mL/min). The end points were bleeding outcomes (Bleeding Academic Research Consortium type 2 or higher), ischemic outcomes (cardiovascular death, myocardial infarction, stent thrombosis, repeated revascularization, and ischemic stroke), and net adverse clinical event (including any clinical event) at 1-year follow-up.
UNASSIGNED: Prasugrel de-escalation was beneficial regardless of baseline renal function (P for interaction = 0.508). The relative reduction in bleeding risk from prasugrel de-escalation was higher in the low eGFR group than in both the intermediate and high eGFR groups (relative reductions, respectively: 64% (HR: 0.36; 95% CI: 0.15-0.83) vs 50% (HR: 0.50; 95% CI: 0.28-0.90) and 52% (HR: 0.48; 95% CI: 0.21-1.13) (P for interaction = 0.646). Ischemic risk from prasgurel de-escalation was not significant in all eGFR groups (HR: 1.18 [95% CI: 0.47-2.98], HR: 0.95 [95% CI: 0.53-1.69], and HR: 0.61 [95% CI: 0.26-1.39]) (P for interaction = 0.119).
UNASSIGNED: In patients with acute coronary syndrome receiving PCI, prasugrel dose de-escalation was beneficial regardless of the baseline renal function.

Hypofibrinolysis is a recently-recognized risk factor for recurrent cardiovascular events in patients with ST-segment elevation myocardial infarction (STEMI), but the mechanistic determinants of this are not well understood. In patients with STEMI, we show that the effectiveness of endogenous fibrinolysis in whole blood is determined in part by fibrinogen level, high sensitivity C-reactive protein, and shear-induced platelet reactivity, the latter directly related to the speed of thrombin generation. Our findings strengthen the evidence for the role of cellular components and bidirectional crosstalk between coagulatory and inflammatory pathways as determinants of hypofibrinolysis.

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UNASSIGNED: Cocaine use is a well-established risk factor for acute coronary syndrome (ACS) although other recreational drugs (RD), are increasingly considered as potential cardiac risk factors. Compared to ACS without RD use, worse outcomes have been described for RD-associated ACS.
UNASSIGNED: The aim of this study was to explore the use of RD in a contemporary cohort of young ACS patients.
UNASSIGNED: Between June 2016 and October 2019, ACS patients aged 18-50 years, admitted to OLVG Hospital in Amsterdam, were retrospectively analysed. Medical chart review was performed to obtain patient and clinical characteristics, RD use, cardiac risk factors, outcome and follow up.
UNASSIGNED: A total of 229 patients were included in the study. Recreational drug use prior to ACS was present in 24.9% of all patients, with cannabis (16.2%), cocaine (4.8%), or both (2.6%) most commonly observed. RD users were predominantly young men (87.7%) and had a significantly higher tobacco use compared to non-RD users (89.5% vs. 62.8%, P < 0.001), also after adjusting for age and sex. RD use was associated with larger myocardial infarctions with significantly higher CK-MB levels (104 ± 116 U/L vs 62 ± 96, P = 0.040) and poorer left ventricular function measured by echocardiography as compared to non-users (P = 0.007).
UNASSIGNED: Recreational drug use was present in almost 25% of all young ACS patients evaluated for drug use and was associated with larger myocardial infarction resulting in poorer left ventricular function as compared to non-users. Additionally, RD-users were younger and were more often tobacco users, compared to non-users.

UNASSIGNED: Nonalcoholic fatty liver disease (NAFLD) is common among patients with type 2 diabetes mellitus (T2DM) and is associated with increased risk for coronary atherosclerosis and acute cardiovascular (CV) events. We employed the validated, non-invasive Angulo NAFLD fibrosis score (FS) in an intervention study in patients with T2DM and recent acute coronary syndrome (ACS) to determine the association of FS with CV risk and treatment response to apabetalone. Apabetalone is a novel selective inhibitor of the second bromodomain of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression.
UNASSIGNED: The Phase 3 BETonMACE trial compared apabetalone with placebo in 2,425 patients with T2DM and recent ACS. In this post hoc analysis, we evaluated the impact of apabetalone therapy on CV risk, defined as a composite of major adverse cardiovascular events (MACE: CV death, non-fatal myocardial infarction [MI], or stroke) and hospitalization for heart failure (HHF) in two patient categories of FS that reflect the likelihood of underlying NAFLD. Patients were initially classified into three mutually exclusive categories according to a baseline Angulo FS <-1.455 (F0-F2), -1.455 to 0.675 (indeterminant), and >0.675 (F3-F4), where F0 through F4 connote fibrosis severity none, mild, moderate, severe, and cirrhosis, respectively. The composite of ischemic MACE and HHF in the placebo group was higher in indeterminant and F3-F4 categories compared to the F0-F2 category (17.2% vs 15.0% vs 9.7%). Therefore, for the present analysis, the former two categories were combined into an elevated NAFLD CVD risk group (FS+) that was compared with the F0-F2 group (lower NAFLD risk, FS0-2).
UNASSIGNED: In 73.7% of patients, FS was elevated and consistent with a moderate-to-high likelihood of advanced liver fibrosis (FS+); 26.3% of patients had a lower FS (FS0-2). In the placebo group, FS+ patients had a higher incidence of ischemic MACE and HHF (15.4%) than FS0-2 patients (9.7%). In FS+ patients, addition of apabetalone to standard of care treatment lowered the rate of ischemic MACE compared with placebo (HR = 0.79; 95% CI 0.60-1.05; p=0.10), HHF (HR = 0.53; 95% CI 0.33-0.86; p=0.01), and the composite of ischemic MACE and HHF (HR = 0.76; 95% CI 0.59-0.98; p=0.03). In contrast, there was no apparent benefit of apabetalone in FS0-2 patients (HR 1.24; 95% CI 0.75-2.07; p=0.40; HR 1.12; 95% CI 0.30-4.14; p=0.87; and HR 1.13; 95% CI 0.69-1.86; p=0.62, respectively). Over a median duration of 26.5 months, FS increased from baseline in both treatment groups, but the increase was smaller in patients assigned to apabetalone than to placebo (p=0.04).
UNASSIGNED: Amongst patients with T2DM, recent ACS, and a moderate-to-high likelihood of advanced liver fibrosis, apabetalone was associated with a significantly lower rate of ischemic MACE and HHF and attenuated the increase in hepatic FS over time.

UNASSIGNED: Sarcoidosis is a chronic inflammatory disorder of unknown etiology associated with high morbidity and mortality. Its association with cardiovascular outcomes is under-documented.
UNASSIGNED: The aim of this study was to assess the adverse cardiovascular outcomes in patients with sarcoidosis compared with that of non-sarcoidosis.
UNASSIGNED: Online databases including PubMed, Embase and Scopus were queried from inception until March 2022. The outcomes assessed included all-cause mortality (ACM) and incidence of ventricular tachycardia (VT), heart failure (HF) and atrial arrhythmias (AA).
UNASSIGNED: A total of 6 studies with 22,539,096 participants (42,763 Sarcoidosis, 22,496,354 Non-Sarcoidosis) were included in this analysis. The pooled prevalence of sarcoidosis was 13.1% (95% CI 1% to 70%). The overall mean age was 47 years. The most common comorbidities were hypertension (12.7% vs 12.5%), and diabetes mellitus (5.5% vs 4%) respectively. The pooled analysis of primary endpoints showed that all-cause mortality (RR, 2.08; 95% CI: 1.17 to 3.08; p = 0.01) was significantly increased in sarcoidosis patients. The pooled analysis of secondary endpoints showed that the incidence of VT (RR, 15.3; 95% CI: 5.39 to 43.42); p < 0.001), HF (RR, 4.96; 95% CI: 2.02 to 12.14; p < 0.001) and AA (RR, 2.55; 95% CI: 1.47 to 4.44); p = 0.01) were significantly higher with sarcoidosis respectively compared to non-sarcoidosis.
UNASSIGNED: Incidence of VT, HF and AA was significantly higher in patients with CS. Clinicians should be aware of these adverse cardiovascular events associated with sarcoidosis.

Genetic predisposition through F11R-single-nucleotide variation (SNV) influences circulatory soluble junctional adhesion molecule-A (sJAM-A) levels in coronary artery disease (CAD) patients. Homozygous carriers of the minor alleles (F11R-SNVs rs2774276, rs790056) show enhanced levels of thrombo-inflammatory sJAM-A. Both F11R-SNVs and sJAM-A are associated with worse prognosis for recurrent myocardial infarction in CAD patients. Platelet surface-associated JAM-A correlate with platelet activation markers in CAD patients. Activated platelets shed transmembrane-JAM-A, generating proinflammatory sJAM-A and JAM-A-bearing microparticles. Platelet transmembrane-JAM-A and sJAM-A as homophilic interaction partners exaggerate thrombotic and thrombo-inflammatory platelet monocyte interactions. Therapeutic strategies interfering with this homophilic interface may regulate thrombotic and thrombo-inflammatory platelet response in cardiovascular pathologies where circulatory sJAM-A levels are elevated.

UNASSIGNED: Clonal hematopoiesis of indeterminate potential (CHIP) is a novel cardiovascular disease (CVD) risk factor in individuals without acute myeloid leukemia (AML).
UNASSIGNED: The aim of this study was to examine the association between mutations associated with CHIP (CHIP-related mutations) identified in patients at AML diagnosis and the risk for cardiovascular events (CVEs).
UNASSIGNED: This was a retrospective cohort study of 623 patients with AML treated between 2015 and 2018 who underwent DNA analysis. Cause-specific hazard regression models were used to study the associations between pathogenic mutations in common CHIP-related genes (DNMT3A, TET2, ASXL1, JAK2, TP53, SRSF2, and SF3B1) and the rate of CVEs (heart failure hospitalization, acute coronary syndrome, coronary artery revascularization, ischemic stroke, venous thromboembolism, and CVD death) and between CVE development and all-cause mortality.
UNASSIGNED: Patients were 64.6 ± 15.3 years of age, 265 (42.5%) were women, and 63% had at least 1 CHIP-related mutation. Those with CHIP-related mutations were older (69.2 ± 12.3 vs 56.6 ± 16.6 years; P < 0.001) and had a greater prevalence of CVD risk factors and CVD history. In adjusted analysis, the presence of any CHIP-related mutation was associated with a higher rate of CVEs (HR: 1.74; 95% CI: 1.03-2.93; P = 0.037) among intensively treated patients (anthracycline based) but not the whole cohort (HR: 1.26; 95% CI: 0.81-1.97; P = 0.31). TP53 (HR: 4.18; 95% CI: 2.07-8.47; P < 0.001) and ASXL1 (HR: 2.37; 95% CI: 1.21-4.63; P = 0.012) mutations were associated with CVEs among intensively treated patients. Interval development of CVEs was associated with all-cause mortality (HR: 1.99; 95% CI: 1.45-2.73; P < 0.001).
UNASSIGNED: Among patients with AML treated with intensive chemotherapy, mutations in CHIP-related genes were associated with an increased risk for developing incident CVEs after AML diagnosis.