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4/18/26

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

23:28

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

23:28

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