Browsing by Subject "RISK"
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Item Open Access Association of elevated serumfree light chains with chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis.(Blood cancer journal, 2019-08-05) Clay-Gilmour, Alyssa I; Rishi, Abdul R; Goldin, Lynn R; Greenberg-Worisek, Alexandra J; Achenbach, Sara J; Rabe, Kari G; Maurer, Matthew J; Kay, Neil E; Shanafelt, Tait D; Call, Timothy G; Brice Weinberg, J; Camp, Nicola J; Cerhan, James R; Leis, Jose; Norman, Aaron; Murray, David L; Vincent Rajkumar, S; Caporaso, Neil E; Landgren, Ola; McMaster, Mary L; Slager, Susan L; Vachon, Celine MChronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p's < 0.05). However, there were no statistically significant differences in sFLC monoclonal or polyclonal elevations between familial and sporadic CLL cases (p's > 0.05). Unaffected relatives and MBL cases from CLL/MBL families, ages >60 years, showed elevated monoclonal sFLC, compared to the reference population (p's < 0.05). This is the first study to demonstrate monoclonal sFLC elevations in CLL cases compared to controls. Monoclonal sFLC levels may provide additional risk information in relatives of CLL probands.Item Open Access Effect of Lifestyle Changes after Percutaneous Coronary Intervention on Revascularization.(BioMed research international, 2020-01) Wang, Yang; Xian, Ying; Chen, Tao; Zhao, Yanyan; Yang, Jinggang; Xu, Bo; Li, WeiObjective:Whether optimal cardiovascular health metrics may reduce the risk of cardiovascular events in secondary prevention is uncertain. The study was conducted to evaluate the influence of lifestyle changes on clinical outcomes among the subjects underwent percutaneous coronary intervention (PCI). Methods:The study group consists of 17,099 consecutive PCI patients. We recorded data on subject lifestyle behavior changes after their procedure. Patients were categorized as ideal, intermediate, or poor CV health according to a modified Life's Simple 7 score (on body mass, smoking, physical activity, diet, cholesterol, blood pressure, and glucose). Multivariable COX regression was used to evaluate the association between CV health and revascularization event. We also tested the impact of cumulative cardiovascular health score on reoccurrence of cardiovascular event. Results:During a 3-year median follow-up, 1,583 revascularization events were identified. The observed revascularization rate was 8.0%, 9.3%, and 10.6% in the group of patients with optimal (a modified Life's Simple 7 score of 11-14), average (score = 9 or 10), or inadequate (less or equal than 8) CV health, respectively. After multivariable analysis, the adjusted hazard ratios were 0.83 (95% CI: 0.73-0.94) and 0.89 (95% CI: 0.79-0.99) for patients with optimal and average lifestyle changes comparing with the inadequate tertile (P for trend = 0.003). In addition, each unit increase in above metrics was associated with a decrease risk of revascularization (HR, 0.96; 95% confidence interval, 0.93-0.98; P for trend = 0.003). In addition, each unit increase in above metrics was associated with a decrease risk of revascularization (HR, 0.96; 95% confidence interval, 0.93-0.98. Conclusion:Ideal CV health related to lower incidence of cardiovascular events, even after the percutaneous coronary intervention. Revascularization can be reduced by lifestyle changes. The cardiovascular health metrics could be extrapolated to secondary prevention and need for further validation.Item Open Access Evaluation of a Standardized Cardiac Athletic Screening for National Collegiate Athletic Association (NCAA) Athletes.(The western journal of emergency medicine, 2019-08-14) Fischetti, Chanel E; Kamyszek, Reed W; Shaheen, Stephen; Oshlag, Benjamin; Banks, Adam; Blood, AJ; Bytomski, Jeffrey R; Boggess, Blake; Lahham, ShadiINTRODUCTION:Sudden cardiac death is a rare cause of death in young athletes. Current screening techniques include history and physical exam (H and P), with or without an electrocardiogram (ECG). Adding point of care cardiac ultrasound has demonstrated benefits, but there is limited data about implementing this technology. We evaluated the feasibility of adding ultrasound to preparticipation screening for collegiate athletes. METHODS:We prospectively enrolled 42 collegiate athletes randomly selected from several sports. All athletes were screened using a 14-point H and P based on 2014 American College of Cardiology (ACC) and American Heart Association (AHA) guidelines, ECG, and cardiac ultrasound. RESULTS:We screened 11 female and 31 male athletes. On ultrasound, male athletes demonstrated significantly larger interventricular septal wall thickness (p = 0.002), posterior wall thickness (p <0.001) and aortic root breadth (p = 0.002) compared to females. Based on H and P and ECGs alone and a combination of H and P with ECG, no athletes demonstrated a positive screening for cardiac abnormalities. However, with combined H and P, ECG, and cardiac ultrasound, one athlete demonstrated positive findings. CONCLUSIONS:We believe that adding point of care ultrasound to the preparticipation exam of college athletes is feasible. This workflow may provide a model for athletic departments' screening.Item Open Access Incidence, Characteristics, and Outcomes of Myocardial Infarction in Patients With Peripheral Artery Disease: Insights From the EUCLID Trial.(JAMA cardiology, 2019-01) Olivier, Christoph B; Mulder, Hillary; Hiatt, William R; Jones, W Schuyler; Fowkes, F Gerry R; Rockhold, Frank W; Berger, Jeffrey S; Baumgartner, Iris; Held, Peter; Katona, Brian G; Norgren, Lars; Blomster, Juuso; Patel, Manesh R; Mahaffey, Kenneth WImportance:Patients with peripheral artery disease (PAD) are at high risk for myocardial infarction (MI). Objective:To characterize the incidence and types of MI in a PAD population, identify factors associated with MI, and determine the association of MI with cardiovascular mortality and acute limb ischemia. Design, Setting, and Participants:The Study Comparing Cardiovascular Effects of Ticagrelor and Clopidogrel in Patients With Peripheral Artery Disease (EUCLID) was a double-blind randomized clinical trial conducted at 811 sites in 28 countries that randomized 13 885 patients with symptomatic PAD to monotherapy with ticagrelor or clopidogrel. Participants had an ankle-brachial index (ABI) of 0.80 or less or previous lower extremity revascularization. Median follow-up was 30 months. For these analyses, patients were evaluated for MI occurrence during follow-up irrespective of treatment. Data were analyzed from June 2017 to September 2018. Main Outcomes and Measures:An adjudication clinical events committee classified MI as type 1 (spontaneous), type 2 (secondary), type 3 (sudden cardiac death), type 4a (less than 48 hours after percutaneous coronary intervention), type 4b (definite stent thrombosis), or type 5 (less than 72 hours after coronary artery bypass graft). A multivariate regression model was developed by stepwise selection to identify factors associated with MI, and a time-dependent multivariate Cox regression analysis was performed to determine the association of MI with cardiovascular death and acute limb ischemia requiring hospitalization. Results:Of the 13 885 patients included in this analysis, 9997 (72.0%) were male, and the median (interquartile range) age was 66 (60-73) years. Myocardial infarction occurred in 683 patients (4.9%; 2.4 events per 100 patient-years) during a median follow-up of 30 months. Patients experiencing MI were older (median [interquartile range] age, 69 [62-75] vs 66 [60-72] years), more likely to have diabetes (349 of 683 [51.1%] vs 4996 of 13 202 [37.8%]) or a previous lower extremity revascularization (466 of 683 [68.2%] vs 7409 of 13 202 [56.1%]), and had a lower ABI (if included by ABI) compared with censored patients. Of the 683 patients with MI during follow-up, the most common MI type was type 1 (405 [59.3%]), followed by type 2 (236 [34.6%]), type 4a (14 [2.0%]), type 3 (12 [1.8%]), type 4b (11 [1.6%]), and type 5 (5 [0.7%]). Postrandomization MI was independently associated with cardiovascular death (adjusted hazard ratio, 9.0; 95% CI, 7.3-11.2; P < .001) and acute limb ischemia requiring hospitalization (adjusted hazard ratio, 2.5; 95% CI, 1.3-5.0; P = .008). Conclusions and Relevance:Approximately 5% of patients with symptomatic PAD had an MI during a median follow-up of 30 months. Type 1 MI (spontaneous) was the most common MI type; however, one-third of MIs were type 2 MI (secondary). More research is needed to identify therapies to reduce the risk of MI in patients with PAD and to improve management of type 2 MI. Trial Registration:ClinicalTrials.gov Identifier: NCT01732822.Item Open Access Persistent Depressive Symptoms are Independent Predictors of Low-Grade Inflammation Onset Among Healthy Individuals.(Arquivos brasileiros de cardiologia, 2017-06) Franco, Fábio Gazelato de Mello; Laurinavicius, Antonio Gabriele; Lotufo, Paulo A; Conceição, Raquel D; Morita, Fernando; Katz, Marcelo; Wajngarten, Maurício; Carvalho, José Antonio Maluf; Bosworth, Hayden B; Santos, Raul DiasBackground
Depressive symptoms are independently associated with an increased risk of cardiovascular disease (CVD) among individuals with non-diagnosed CVD. The mechanisms underlying this association, however, remain unclear. Inflammation has been indicated as a possible mechanistic link between depression and CVD.Objectives
This study evaluated the association between persistent depressive symptoms and the onset of low-grade inflammation.Methods
From a database of 1,508 young (mean age: 41 years) individuals with no CVD diagnosis who underwent at least two routine health evaluations, 134 had persistent depressive symptoms (Beck Depression Inventory - BDI ≥ 10, BDI+) and 1,374 had negative symptoms at both time points (BDI-). All participants had been submitted to repeated clinical and laboratory evaluations at a regular follow-up with an average of 26 months from baseline. Low-grade inflammation was defined as plasma high-sensitivity C-Reactive Protein (CRP) concentrations > 3 mg/L. The outcome was the incidence of low-grade inflammation evaluated by the time of the second clinical evaluation.Results
The incidence of low-grade inflammation was more frequently observed in the BDI+ group compared to the BDI- group (20.9% vs. 11.4%; p = 0.001). After adjusting for sex, age, waist circumference, body mass index, levels of physical activity, smoking, and prevalence of metabolic syndrome, persistent depressive symptoms remained an independent predictor of low-grade inflammation onset (OR = 1.76; 95% CI: 1.03-3.02; p = 0.04).Conclusions
Persistent depressive symptoms were independently associated with low-grade inflammation onset among healthy individuals.Item Open Access The effects of depression and use of antidepressive medicines during pregnancy on the methylation status of the IGF2 imprinted control regions in the offspring.(Clinical epigenetics, 2011-10-26) Soubry, A; Murphy, Sk; Huang, Z; Murtha, A; Schildkraut, Jm; Jirtle, Rl; Wang, F; Kurtzberg, J; Demark-Wahnefried, W; Forman, Mr; Hoyo, CIn utero exposures to environmental factors may result in persistent epigenetic modifications affecting normal development and susceptibility to chronic diseases in later life. We explored the relationship between exposure of the growing fetus to maternal depression or antidepressants and DNA methylation at two differentially methylated regions (DMRs) of the imprinted Insulin-like Growth Factor 2 (IGF2) gene. Aberrant DNA methylation at the IGF2 and neighboring H19 DMRs has been associated with deregulated IGF2 expression, childhood cancers and several chronic diseases during adulthood. Our study population is comprised of pregnant mothers and their newborns (n = 436), as part of the Newborn Epigenetics Study (NEST). A standardized questionnaire was completed and medical record data were abstracted to ascertain maternal depression and antidepressive drug use. DMR methylation levels in umbilical cord blood leukocytes were quantified using pyrosequencing. From the 436 newborns, laboratory data were obtained for 356 individuals at the IGF2 DMRs, and for 411 individuals at the H19 DMRs; about half of each group was African American or Caucasian. While overall no association between depression and methylation profiles was found, we observed a significant hypermethylation of the H19 DMRs in newborns of African American (n = 177) but not Caucasian (n = 168) mothers who reported the use of antidepressive drugs during pregnancy (β = +6.89, p = 0.01). Of note, our data reveal a race-independent association between smoking during pregnancy and methylation at the IGF2 DMR (+3.05%, p = 0.01). In conclusion, our findings suggest a race-dependent response related to maternal use of antidepressants at one of the IGF2 DMRs in the offspring.Item Open Access Validation of a Model Predicting De Novo Stress Urinary Incontinence in Women Undergoing Pelvic Organ Prolapse Surgery.(Obstetrics and gynecology, 2019-04) Jelovsek, J Eric; van der Ploeg, J Marinus; Roovers, Jan-Paul; Barber, Matthew DOBJECTIVE:To validate a previously developed prediction model for de novo stress urinary incontinence (SUI) after undergoing vaginal surgery for pelvic organ prolapse (POP). METHODS:Model performance was determined using a cohort of women who participated in two, 14-center randomized trials in the Netherlands that evaluated whether postoperative SUI 1 year after surgery was reduced with or without concomitant midurethral sling at the time of surgery for symptomatic women who had at least stage 2 POP. Age, number of previous vaginal births, urine leakage associated with urgency, history of diabetes, body mass index, preoperative stress test result, and placement of a midurethral sling were used to calculate the predicted probability of an individual developing de novo SUI. Predicted probabilities were compared with outcomes and quantitated using the concordance index and calibration curves. Model accuracy was compared with and without the preoperative stress test, and net reclassification improvement was measured using probability cutoffs of 0.2, 0.3, and 0.4. RESULTS:Of 239 participants who did not report preoperative SUI and underwent surgery, 152 were eligible for analysis with complete baseline and outcome data. Model discrimination was acceptable and consistent with performance in the original development cohort when the preoperative stress test result was included (concordance index 0.63; 95% CI 0.52-0.74) and had lower discrimination than when the stress test variable was not included (concordance index 0.57; 95% CI 0.46-0.67, P=.048). The model that included the stress test variable was most accurate when predicted probabilities of de novo SUI were between 0 and 50%, and it correctly reclassified upward 5.9% (95% CI -14.8 to 26.8) of participants with de novo SUI and correctly reclassified downward 16.9% (95% CI 6.6-27.7) of participants without de novo SUI. CONCLUSION:On external validation, the model was predictive of de novo SUI after vaginal prolapse surgery and may facilitate decision making regarding concomitant sling placement. CLINICAL TRIAL REGISTRATION:Nederlands Trial Register, NTRR 1197 en 1070.