ABSTRACT

Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.

PMID:37532724 | DOI:10.1038/s41467-023-39521-2

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PubMed articles on: Cancer & VTE/PE

Prevalence of and Eligibility for Surveillance Without Anticoagulation Among Adults With Lower-Risk Acute Subsegmental Pulmonary Embolism

JAMA Netw Open. 2023 Aug 1;6(8):e2326898. doi: 10.1001/jamanetworkopen.2023.26898.

ABSTRACT

IMPORTANCE: Approximately 8% of acute pulmonary emboli are confined to the subsegmental arteries. The 2016 and 2021 American College of Chest Physicians (CHEST) guidelines and expert panel reports suggest the use of structured surveillance without anticoagulation for select ambulatory patients with subsegmental pulmonary embolism who do not have active cancer, deep vein thrombosis, impaired cardiopulmonary reserve, marked symptoms, or increased risk of recurrent venous thromboembolism; however, guideline uptake in community practice is unknown, as is the proportion of outpatients eligible for surveillance.

OBJECTIVE: To describe the prevalence of surveillance among outpatients with acute subsegmental pulmonary embolism and to estimate the proportion of patients eligible for structured surveillance using modified CHEST criteria.

DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study was conducted across 21 US community hospitals in the Kaiser Permanente Northern California integrated health system from January 1, 2017, to December 31, 2021. Adult outpatients with acute subsegmental pulmonary embolism were included. Patients with the following higher-risk characteristics were excluded: codiagnoses requiring hospitalization, non-low-risk vital signs (ie, systolic blood pressure <90

MAIN OUTCOMES AND MEASURES: The main outcomes were the (1) prevalence of surveillance and (2) eligibility for surveillance using 2 sets of criteria: the CHEST criteria modified by excluding patients with higher-risk characteristics or right ventricular dysfunction and a stricter set of criteria requiring age younger than 65 years and no more than 1 embolus. The prevalence of structured surveillance was calculated and the proportion of patients eligible for surveillance was estimated.

RESULTS: Of the 666 outpatients with acute subsegmental pulmonary embolism included in this study, 229 with lower-risk characteristics were examined. Their median age was 58 (IQR, 42-68) years; more than half were men (120 [52.4%]) and self-identified as non-Hispanic White (128 [55.9%]). Six patients (2.6%) were initially not treated with anticoagulants. Among the lower-risk cohort, only 1 patient (0.4% [95% CI, 0.01%-2.4%]) underwent structured surveillance, without 90-day sequelae. Thirty-five patients (15.3% of the lower-risk group and 5.3% of the full cohort) were surveillance eligible using modified CHEST criteria. Fifteen patients (6.6% of the lower-risk group and 2.3% of the full cohort) were surveillance eligible using stricter criteria.

CONCLUSIONS AND RELEVANCE: In this cohort study of lower-risk outpatients with subsegmental pulmonary embolism, few were eligible for structured surveillance, and only a small proportion of eligible patients underwent surveillance despite the CHEST guideline. If forthcoming trials find surveillance safe and effective, substantial uptake into clinical practice may require more than passive diffusion.

PMID:37531107 | DOI:10.1001/jamanetworkopen.2023.26898

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PubMed articles on: Cancer & VTE/PE

A novel risk prediction score for clinically significant bleeding in patients anticoagulated for venous thromboembolism with active cancer

Thromb Haemost. 2023 Aug 1. doi: 10.1055/a-2145-7238. Online ahead of print.

ABSTRACT

BACKGROUND: Cancer associated venous thromboembolism (Ca-VTE) treatment with anticoagulation is associated with bleeding complications and there are limited data on risk factors. Current models do not provide accurate bleeding risk prediction.

METHODS: UK Clinical Practice Research Datalink data (2008-2020) was used to generate a cohort of patients with anticoagulant initiation for first Ca-VTE. Patients were observed up to 180 days for significant bleeding including major bleeding, and clinically relevant non-major bleeding requiring hospitalisation (CRNMB-H). A scoring scheme was developed from subdistribution hazard ratios, and its discrimination (expressed by the C-statistic) estimated from cross-validation.

RESULTS: 15,749 patients with Ca-VTE and anticoagulant treatment were included. In total, 537 significant bleeding events, 161 major bleeds and 376 CRNMB-H were identified after adjudicated review in 4914 person-years of observation. Incidence rates of 3.3 and 7.7 per 100 person-years were noted for major bleeding and CRNMB-H. Independent predictors of significant bleeding were cancer of the bladder, central nervous system, cervix, kidney, melanoma, prostate and upper gastrointestinal tract. Overall C-statistic for significant bleeding was 0.70, and 0.76 and 0.67 for major bleeding and for CRNMB-H, respectively.

CONCLUSIONS: This risk score may identify patients at risk of significant bleeding, while also helping to determine treatment duration.

PMID:37527782 | DOI:10.1055/a-2145-7238

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PubMed articles on: Cancer & VTE/PE

Intravascular Tumor Extension and Pulmonary Tumor Embolism in Children With Solid Malignancies: Is There a Role for Inferior Vena Cava Filters?

J Pediatr Hematol Oncol. 2023 Jul 27. doi: 10.1097/MPH.0000000000002731. Online ahead of print.

ABSTRACT

Intravascular tumor extension is an uncommon complication of solid malignancies that, when present in the inferior vena cava (IVC), can result in fatal pulmonary tumor embolism. Currently, neoadjuvant chemotherapy and surgery are the mainstays of treatment; however, there are no consensus guidelines for management. We describe three cases of pediatric solid malignancies with associated IVC extension and pulmonary tumor embolism. We hypothesize that there is scope for IVC filter placement in such cases to mitigate the risk of fatal pulmonary tumor embolism.

PMID:37526419 | DOI:10.1097/MPH.0000000000002731

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PubMed articles on: Cancer & VTE/PE

Comparative Efficacy of Direct Oral Anticoagulants and Low-Molecular-Weight Heparin in Cancer-Associated Thromboembolism: A Systematic Review and Meta-Analysis

Cureus. 2023 Jun 28;15(6):e41071. doi: 10.7759/cureus.41071. eCollection 2023 Jun.

ABSTRACT

Patients diagnosed with cancer often experience an abnormal occurrence of venous thromboembolism (VTE) and its related complications. In order to evaluate the safety and effectiveness of both treatment approaches, we conducted a comprehensive systematic review and meta-analysis within the realm of cancer-associated thromboembolism. A thorough search was conducted across PubMed, the Cochrane Library, and Embase databases to find studies comparing direct oral anticoagulants (DOACs) with low molecular weight heparins (LMWHs) for the treatment of VTE in patients with malignancy. The analyses utilized the random-effects model. This meta-analysis included 11 studies. The results showed that DOACs were associated with a significantly reduced risk of VTE recurrence (RR: 0.67; 95% CI: 0.55, 0.81, p<0.0001;<0.0001;

PMID:37519604 | PMC:PMC10375513 | DOI:10.7759/cureus.41071

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PubMed articles on: Cancer & VTE/PE

Incidence and Factors Associated With Pulmonary Embolism After Upper Extremity Trauma: A Tertiary Hospital Experience in Turkey

Cureus. 2023 Jun 28;15(6):e41077. doi: 10.7759/cureus.41077. eCollection 2023 Jun.

ABSTRACT

Introduction Venous thromboembolism (VTE), particularly pulmonary embolism (PE), is the third highest cause of death in trauma patients who survive beyond the first day. Musculoskeletal surgery is associated with several complications, some of which may be life-threatening, including deep vein thrombosis (DVT) and PE. Objective This research aims to describe risk variables for VTE after upper extremity (UE) fracture at a single institution and estimate the incidence of PE following UE fracture. Methods The writers accessed the database via their respective universities using the International Standard Classification (ICD) codes. The medical files of patients aged 18 and older who sought treatment at our emergency department for an injury to their UE and also sought treatment at the orthopedics and traumatology clinic between the years 2013 and 2021 were manually scanned. The patients who applied to the Chest Diseases Clinic within 30 days after the trauma and were diagnosed with PE in the ICD code scan were included in the study. Results UE trauma was the cause of admission to the emergency department for 3,265 patients, and 21 of those patients (0.64%) were found to have PE. Fifteen of the patients were male, and six were female. The median age was 59 years (IQR 17). There were no deaths associated with PE. One of the patients had a scaphoid fracture, seven patients had a humerus fracture, five patients had a distal radius fracture, two patients had an acromioclavicular joint injury, one patient had a shoulder dislocation, one patient had a finger fracture, four patients had wrist crush injury. Three patients had diabetes mellitus. Five patients were active smokers. JAK-2 gene V617F mutation was detected in one patient. One patient was diagnosed with prostate cancer, and one had gastric cancer. One patient had a central venous catheter. Two patients were being treated for hypothyroidism. Two patients had hypertension. Conclusion According to the findings of our research, the probability of developing PE in the days following of an injury to the UE was found to be 0.64%. Patients with UE injuries who are active smokers and who also have diabetes, hypertension, hypothyroidism, cancer, coagulation disorder (JAK2 gene V617F mutation), or a central venous catheter may benefit from anticoagulant prophylaxis. This is because these patients are at a higher risk of developing dangerous blood clots.

PMID:37519534 | PMC:PMC10375827 | DOI:10.7759/cureus.41077

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PubMed articles on: Cancer & VTE/PE

Tissue factor positive microparticles as a biomarker for increased risk of breast cancer-associated thrombosis: a mini review

Curr Opin Hematol. 2023 Sep 1;30(5):180-185. doi: 10.1097/MOH.0000000000000774.

ABSTRACT

PURPOSE OF REVIEW: Cancer-associated thrombosis (CAT), such as venous thromboembolism (VTE), is a frequent complication in cancer patients, resulting in poor prognosis. Breast cancer is not highly thrombogenic but is highly prevalent, resulting in increased VTE cases. Many cancers express tissue factor (TF), a glycoprotein that triggers coagulation. The cancer cells were shown to express and release substantial amounts of TF-positive microparticles (MPTF), associated with a prothrombotic state. This narrative review evaluated the current use of the procoagulant MPTF as a biomarker for thrombosis risk in breast cancer.

RECENT FINDINGS: Tumors of epithelial origin with elevated TF expression have been associated with increased VTE incidence. Thus, studies have affirmed the use of MPTF biomarkers for VTE risk in many cancers. Patients with metastatic breast cancer and CAT were found to exhibit elevated procoagulant microparticles in vitro, due to TF expression. The silencing of TF was associated with decreased microparticle release in breast carcinoma cell lines, associated with decreased coagulation.

SUMMARY: CAT is a multifactorial condition, with several various underlying diseases. It is proposed that MPTF may be an effective biomarker for thrombosis risk in breast cancer patients but requires a more systemic evaluation utilizing standardized quantification methods.

PMID:37522480 | DOI:10.1097/MOH.0000000000000774

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PubMed articles on: Cancer & VTE/PE

Estrogen-based hormonal therapy and the risk of thrombosis in COVID-19 patients

Eur J Haematol. 2023 Jul 30. doi: 10.1111/ejh.14061. Online ahead of print.

ABSTRACT

OBJECTIVE: Estrogen-containing contraceptives and hormone replacement therapy are used commonly, however, the risks of venous and arterial thrombosis imparted by such medications during COVID-19 infection or other similar viral infections remain undescribed.

METHODS: To assess the risk of venous and arterial thrombosis in patients receiving oral estrogen-containing therapy (ECT) with COVID-19 as compared to those receiving non-estrogen-based hormonal therapy, we conducted a multicenter cohort study of 991 patients with confirmed COVID-19 infection, 466 receiving estrogen-containing hormonal therapy, and 525 receiving progestin-only or topical therapy.

RESULTS: The use of estrogen-containing therapy was found to significantly increase the risk of venous thromboembolism (VTE) following COVID-19 diagnosis after controlling for age (HR 5.46 [95% CI 1.12-26.7, p = .036]). This risk was highest in patients over age 50, with 8.6% of patients receiving estrogen-containing therapy diagnosed with VTE compared to 0.9% of those receiving non-estrogen-based therapies (p = .026). The risk of arterial thrombosis was not significantly associated with oral estrogen use.

CONCLUSIONS: These results suggest that estrogen-containing therapy is associated with a significantly increased risk of VTE in COVID-19 patients, especially in older individuals. These findings may guide provider counseling and management of patients with COVID-19 on estrogen-containing therapy.

PMID:37519103 | DOI:10.1111/ejh.14061

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PubMed articles on: Cancer & VTE/PE

How to Treat Today? Oral and Facial Cancer-Associated Venous Thromboembolism

Pharmaceuticals (Basel). 2023 Jul 17;16(7):1011. doi: 10.3390/ph16071011.