Incidence and Risk of Various Types of Arterial Thromboembolism in Patients With Cancer

ObjectiveTo describe the temporal association and identify risk factors between cancer diagnosis and various types of arterial thromboembolism (ATE).Patients and MethodsWe inquired an aggregated electronic health record database (Explorys, IBM Corp., Armonk, New York) and identified patients with cancer from January 1999 to October 2019, with various types of ATE, including myocardial infarction, acute ischemic stroke, acute limb ischemia, acute mesenteric ischemia, acute renal infarction, and retinal artery occlusion. We investigated the temporal relationship between cancer diagnosis and ATE events by examining the incidence ratio (IR) of ATE before and after diagnosis of cancer.ResultsWe identified 305,384 patients with cancer and ATE. The 30-day interval IR of total ATE was elevated shortly before and after cancer diagnosis, which was consistent among different ATE and cancer types. The incidence was highest within a 330-day window (90 days before and 240 days after cancer diagnosis), and IR peaked at 13.9 (95% confidence interval [CI], 13.6 to 14.2) in the first 30 days following diagnosis of cancer. Compared with patients with cancer who never developed ATE, patients with ATE had more cardiovascular risk factors at baseline. Patients with brain cancer, lung cancer, colorectal cancer, and pancreatic cancer had the highest risk of developing ATE, whereas ATE type was anatomically associated with cancer type.ConclusionIn this observational study of an aggregated US patient population, those with newly diagnosed cancer had increased risk of ATE events. This risk was most elevated in a 330-day window around cancer diagnosis and was consistent across different types of ATE and cancer.     

Clinical Characteristics and Outcomes of Patients With Primary Plasma Cell Leukemia in the Era of Novel Agent Therapy

ObjectiveTo evaluate the clinical outcomes of patients with primary plasma cell leukemia (pPCL) defined by 5% or greater clonal circulating plasma cells on peripheral blood smear and treated with novel agent induction therapies.Patients and MethodsA cohort of 68 patients with pPCL diagnosed at the Mayo Clinic in Rochester, Minnesota, from January 1, 2000, to December 31, 2019, and treated with novel agent induction therapies was evaluated.ResultsThe median follow-up was 46 (95% CI, 41 to 90) months. The median bone marrow plasma cell content was 85% (range, 10% to 100%) and median clonal circulaitng plasma cell percentage on the peripheral blood smear was 26% (range, 5% to 93%). There was a preponderance of t(11;14) primary cytogenetic abnormality in this cohort. The median time to next therapy (TTNT) and overall survival (OS) for all patients with pPCL patients in this cohort was 13 (95% CI, 9 to 17) and 23 (95% CI, 19 to 38) months, respectively. However, when stratified by cytogenetic risk, the median TTNT and OS were 16 and 51 months for standard risk vs 9 and 19 months for high risk (P=.01 for OS).ConclusionPrimary plasma cell leukemia remains an aggressive disease with poor prognosis despite novel agent–based therapies. Some patients have better than expected survival and this phenomenon may be influenced by the absence of high-risk cytogenetics. Newer treatment regimens are needed to improve the prognosis of this devastating disease.     

Ratio between Vena Contracta Width and Tricuspid Annular Diameter: Prognostic Value in Secondary Tricuspid Regurgitation

STR = secondary tricuspid regurgitation; TA = tricuspid annulus; VC = vena contracta

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Longitudinal Anthropometric Measures and Risk of New-Onset Atrial Fibrillation Among Community-Dwelling Men and Women

ObjectiveTo assess the sex-specific evolution of various anthropometric measures and the association of their longitudinal trajectories with new-onset atrial fibrillation (AF).MethodsAmong 5266 men and 7218 women free of AF at baseline from the prospective population-based Rotterdam Study, each anthropometric measure was measured 1 to 5 times from 1989 to 2014. Anthropometric measures were standardized to obtain hazard ratios per 1 SD increase to enable comparison. Joint models were used to assess the longitudinal association between anthropometric measures and incident AF. Use of the joint models is a preferred method for simultaneous analyses of repeated measurements and survival data for conferring less biased estimates.ResultsMean (SD) age was 63.9 (8.9) years for men and 64.9 (9.8) years for women. Median follow-up time was 10.5 years. Longitudinal evolution of weight, height, waist circumference, hip circumference, and body mass index was associated with an increased risk of new-onset AF in both men and women. In joint models, larger height in men (hazard ratio [95% credible interval] per 1 SD, 1.27 [1.17 to 1.38]) and weight in women (1.24 [1.16 to 1.34]) showed the largest associations with AF. In joint models, waist to hip ratio was significantly associated with incident AF only in women (1.10 [1.03 to 1.18]).ConclusionConsidering the entire longitudinal trajectories in joint models, anthropometric measures were positively associated with an increased risk for new-onset AF among men and women in the general population. Increase in measure of central obesity showed a stronger association with increased risk of AF onset among women compared with men.     

Association of Self-reported Walking Pace With Type 2 Diabetes Incidence in the UK Biobank Prospective Cohort Study

ObjectiveTo investigate the association between self-reported walking pace and type 2 diabetes (T2D) incidence and whether it differed by physical activity levels and walking time.MethodsThere were 162,155 participants (mean age, 57.1 years; 54.9% women) from the UK Biobank prospective study, recruited between 2006 and 2010, included in the study. Walking pace was self-reported and classified as brisk, average, or slow. Total physical activity and walking time were self-reported using the International Physical Activity Questionnaire. Association between walking pace and T2D incidence and the potential moderating role of physical activity and walking time were investigated using Cox proportional hazards models.ResultsThe median follow-up was 7.4 (interquartile range, 6.7 to 8.2) years. There were 4442 participants in whom T2D developed during the follow-up period. In the fully adjusted model (sociodemographic factors, diet, body mass index, and physical activity), average walking pace (hazard ratio [HR], 1.28; 95% CI, 1.14 to 1.44) and slow walking pace (HR, 1.91; 95% CI, 1.62 to 2.24) were associated with a higher T2D risk compared with brisk walking among women. Among men, average walking pace (HR, 1.28; 95% CI, 1.17 to 1.40) and slow walking pace (HR, 1.73; 95% CI, 1.50 to 1.99) were also associated with higher T2D risk. Compared with slow walkers, brisk walkers have the same diabetes incidence rate 18.6 and 16.0 years later, for women and men, respectively.ConclusionAverage and slow walking pace was associated with a higher risk of incident T2D in both men and women, independent of major confounding factors. The associations were consistent across different physical activity levels and walking time.     

An Electronic Health Record–Compatible Model to Predict Personalized Treatment Effects From the Diabetes Prevention Program: A Cross-Evidence Synthesis Approach Using Clinical Trial and Real-World Data

ObjectiveTo develop an electronic health record (EHR)-based risk tool that provides point-of-care estimates of diabetes risk to support targeting interventions to patients most likely to benefit.Patients and MethodsA risk prediction model was developed and validated in a large observational database of patients with an index visit date between January 1, 2012, and December 31, 2016, with treatment effect estimates from risk-based reanalysis of clinical trial data. The risk model development cohort included 1.1 million patients with prediabetes from the OptumLabs Data Warehouse (OLDW); the validation cohort included a distinct sample of 1.1 million patients in OLDW. The randomly assigned clinical trial cohort included 3081 people from the Diabetes Prevention Program (DPP) study.ResultsEleven variables reliably obtainable from the EHR were used to predict diabetes risk. This model validated well in the OLDW (C statistic = 0.76; observed 3-year diabetes rate was 1.8% (95% confidence interval [CI], 1.7 to 1.9) in the lowest-risk quarter and 19.6% (19.4 to 19.8) in the highest-risk quarter). In the DPP, the hazard ratio (HR) for lifestyle modification was constant across all levels of risk (HR, 0.43; 95% CI, 0.35 to 0.53), whereas the HR for metformin was highly risk dependent (HR, 1.1; 95% CI, 0.61 to 2.0 in the lowest-risk quarter vs HR, 0.45; 95% CI, 0.35 to 0.59 in the highest-risk quarter). Fifty-three percent of the benefits of population-wide dissemination of the DPP lifestyle modification and 73% of the benefits of population-wide metformin therapy can be obtained by targeting the highest-risk quarter of patients.ConclusionThe Tufts–Predictive Analytics and Comparative Effectiveness DPP Risk model is an EHR-compatible tool that might support targeted diabetes prevention to more efficiently realize the benefits of the DPP interventions.     

Left Internal Mammary Artery as an Endocrine Organ: Insights Into Graft Biology and Long-term Impact Following Coronary Artery Bypass Grafting

The left internal mammary artery (LIMA) is considered the criterion standard vessel for use in coronary artery bypass grafting. In recent decades, countless studies have documented its superiority over other arterial and venous coronary artery bypass grafting conduits, although the full mechanisms for this superiority remain unknown. A growing body of literature has unveiled the importance of extracellular vesicles known as exosomes in cardiovascular signaling and various pathologic states. In this review, we briefly compare the clinical longevity of the LIMA relative to other conduits, explore the effects of varying grafting techniques on clinical and angiographic outcomes, and provide physiologic insights into graft function on a cellular and molecular level. Finally, we explore exosome signaling as it pertains to atherosclerosis in support of the LIMA as an “endocrine organ.”     

Clinical Outcomes of Adults With Bicuspid Aortic Valve: A European Perspective

ObjectiveTo describe the clinical history of patients with a wide age range diagnosed with bicuspid aortic valve (BAV) and no surgical indication and to evaluate the long-term outcome of patients with BAV referred for elective surgery.Patients and MethodsBetween 2005 and 2017, 350 consecutive patients with no surgical indication (surveillance group, mean age 53±16, 71% men) and 191 with a surgical indication (surgical group, mean age 59±13, 71% men) were prospectively included. Median follow-up was 80 (32 to 115) months.ResultsIn the surveillance group, the 5-year and 10-year survival rates were 93±1% and 89±2%, respectively, with a relative survival of patients with BAV compared with an age- and sex-matched control population of 98.7%. During follow-up, the cumulative 10-year incidence of aortic valve and aorta surgery was high; of 35±4%, the incidence of native valve infective endocarditis (IE) of 0.2% per patient-year, and no cases of aortic dissection were observed. In the surgical group, the 5-year and 10-year survival rates were 97±1% and 89±3%, respectively, with a relative survival of 99.4% compared with the general population. The incidence of IE was 0.4% per patient-year, and no cases of aortic dissection were observed.ConclusionThis regional cohort shows that the 10-year survival rates of patients with BAV and a wide age range, but mostly middle-aged adults, were similar to those of the general population with a very low rate of complications. Adherence to prophylactic surgical indications and younger age might have contributed to this lack of difference.