Quality of life outcomes for patients with metastatic castration-resistant prostate cancer and pretreatment prognostic score.

BACKGROUND: A prognostic risk score (Halabi score) in metastatic castration-resistant prostate cancer (mCRPC) accurately predicts overall survival, but its association with quality of life (QOL) has not been defined. We hypothesize that a higher pretreatment Halabi score is associated with worse QOL outcomes over time in mCRPC patients. METHODS: Patient-level data from the docetaxel plus prednisone control arm of Mainsail, a Phase 3 clinical trial in mCRPC were accessed via ProjectDataSphere. Pretreatment Halabi score included disease-related factors: metastatic site, opioid use, Eastern Cooperative Oncology Group performance status (ECOG-PS), alkaline phosphatase, albumin, hemoglobin, lactic acid dehydrogenase, and PSA, with higher score indicating worse survival. Three QOL scales were created: Functional Assessment of Cancer Therapy-Prostate (FACT-P, higher score = better QOL), Brief Pain Inventory-Short Form Severity score (BPI-SFSS, higher score = higher pain severity), and BPI-SF Interference score (BPI-SFIS, higher score = greater pain interference). Mixed linear model was used to estimate the associations between Halabi score and QOL scores assessed at different time points (baseline, 2 months, and 6 months). RESULTS: This analysis included 412 mCRPC patients (median age = 68 years, 82% white, 5% Black, median log PSA = 4.4 ng/mL). After multivariable adjustment, Halabi score was significantly associated with QOL scores at all time points. At 6 months, multivariable adjusted FACT-P decreased by 10.0 points (worsening), BPI-SFSS increased by 0.8 points (worsening), and BPI-SFIS increased by 0.9 points (worsening) for each unit increase in Halabi risk score. In multivariable analysis of individual components, ECOG-PS, site of metastasis, and opioid use were significantly associated with worse QOL scores at baseline. CONCLUSIONS: Chemotherapy-naïve mCRPC patients with poorer Halabi prognostic risk scores have poorer QOL and greater pain intensity and interference at baseline and during follow-up.

Efficacy and safety of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers: a meta-analysis of randomized controlled trials.

BACKGROUND: Immune checkpoint inhibitors (ICI) have revolutionized care in oncology with improved overall survival in several cancer populations. Nivolumab has recently been approved for use in patients with upper gastrointestinal cancers. We quantitatively summarized the efficacy and safety of Nivolumab use in patients with advanced esophageal, gastroesophageal, and gastric carcinoma compared to standard chemotherapy. METHODS: Systemic search of electronic databases was performed to analyze phase III randomized controlled trials (RCTs) comparing Nivolumab versus standard chemotherapy in patients with advanced upper gastrointestinal cancers. Primary endpoints were overall survival (OS) and progression-free survival (PFS). Data were pooled using random effects model via RevMan 5.4 software. RESULTS: Four RCTs with a total of 3369 patients and a median follow-up of 13 months were included. The patients' mean age was 61 ± 20 years, 74.6% were males, and 26% had ≥1% PD-L1 expression. Compared to the chemotherapy group, Nivolumab group had a significantly favorable OS and PFS [HR 0.81;95% CI (0.74, 0.89), p < .001], [HR 0.82;95% CI (0.69, 0.98), p = .03], respectively. Nivolumab significant effect was only in patients with ≥1% PD L1 expression [HR 0.72; 95% CI (0.58, 0.89), p < .001]. No statistical difference was detected between groups regarding serious adverse effects (AE) [OR 1.47; 95%CI (0.94,2.31), p = 0.09]. CONCLUSIONS: Compared to standard chemotherapy, the use of Nivolumab in patients with advanced esophageal, gastroesophageal, and gastric cancers is associated with improved overall and progression-free survival, with similar rates of AE and AE leading to death. The improvement in survival was significant in patients with ≥1% PD L1 expression.

The Impact of Night-time Emergency Department Presentation on Upper Gastrointestinal Hemorrhage Outcomes.

GOALS: The aim was to investigate the impact of night-time emergency department (ED) presentation on outcomes of patients admitted for acute upper gastrointestinal hemorrhage (UGIH). BACKGROUND: The relationship between time of ED presentation and outcomes of gastrointestinal hemorrhage is unclear. STUDY: Using the 2016 and 2017 Florida State Inpatient Databases which provide times of ED arrival, we identified and categorized adults hospitalized for UGIH to daytime (07:00 to 18:59 h) and night-time (19:00 to 06:59 h) based on the time of ED presentation. We matched both groups with propensity scores, and assessed their clinical outcomes including all-cause in-hospital mortality, in-hospital endoscopy utilization, length of stay (LOS), total hospitalization costs, and 30-day all-cause readmission rates. RESULTS: Of the identified 38,114 patients with UGIH, 89.4% (n=34,068) had acute nonvariceal hemorrhage (ANVH), while 10.6% (n=4046) had acute variceal hemorrhage (AVH). Compared with daytime patients, ANVH patients admitted at night-time had higher odds of in-hospital mortality (odds ratio: 1.32; 95% confidence interval: 1.06-1.60), lower odds of in-patient endoscopy (odds ratio: 0.83; 95% confidence interval: 0.77-0.90), higher total hospital costs ($9911 vs. $9545, P <0.016), but similar LOS and readmission rates. Night-time AVH patients had a shorter LOS (5.4 vs. 5.8 d, P =0.045) but similar mortality rates, endoscopic utilization, total hospitalization costs, and readmission rates as daytime patients. CONCLUSIONS: Patients arriving in the ED at night-time with ANVH had worse outcomes (mortality, hospitalization costs, and endoscopy utilization) compared with daytime patients. However, those with AVH had comparable outcomes irrespective of ED arrival time.

Cluster-randomized controlled trial of intermittent preventive treatment in infancy using sulfadoxine-pyrimethamine (SP-IPTi): a pilot study in Nigeria.

BACKGROUND: Malaria kills a child in sub-Saharan Africa every 2 min despite widely available interventions including intermittent preventive treatment in infants (IPTi). Since 2010, when World Health Organization (WHO) recommended IPTi, no country has implemented it. To our knowledge, no IPTi study has been conducted in Nigeria. Considering severity of malaria in infancy and urgency to improve malaria prevention, we proposed a study to investigate the efficacy of this intervention in reducing malarial morbidity and mortality. OBJECTIVE(S): The aim of this was to determine the safety and efficacy of SP-IPTi in reducing the prevalence of asymptomatic malaria parasitemia and malarial-associated hospital admissions. METHODS: We performed a cluster-randomized controlled trial in 1379 infants. SP was administered alongside routine vaccinations in immunization centers randomized to intervention groups. Infants in control groups received only routine vaccines. Malarial 'morbidity and adverse events were monitored through passive case-detection and cross-sectional surveys'. RESULTS: SP-IPTi was safe. There was no statistically significant difference in terms of risks of asymptomatic parasitemia at 9 months, fever or hospitalization between our control and intervention groups. CONCLUSIONS: Our study demonstrated that SP-IPTi had no benefit but was well tolerated. WHO and some researchers have also reported declining efficacy of SP, due to increasing drug resistance.

Team-based approach to improving medication reconciliation rates in family medicine residency clinics.

OBJECTIVE: The objective of this quality improvement project was to design and implement a systematic team-based care approach to medication reconciliation, with a goal of physician-documented medication reconciliation at 70% of all patient office visits. SETTING: Ambulatory clinics located in urban, underserved communities in Minneapolis and St. Paul, MN. PRACTICE DESCRIPTION: Four family medicine residency clinics, with pharmacists integrated at each site. All clinics use the Epic electronic medical record (Epic Systems Corporation). PRACTICE INNOVATION: A team-based care approach to medication reconciliation was designed and implemented involving medical assistants (MAs), physicians, and pharmacists. The MAs did an initial review with patients, the physicians addressed discrepancies, and difficult situations were escalated to the pharmacist for a detailed assessment. EVALUATION: The percentage of visits with physician-documented medication reconciliation was measured preintervention and then for 18 months postintervention in 6-month intervals involving more than 118,000 patient visits. Satisfaction surveys of team members were done pre- and postintervention. RESULTS: The percentage of visits with physician-documented medication reconciliation improved significantly from 6.5% preintervention to 58.7% (P < 0.001) postintervention, and was sustained and further improved to 70.3% (P < 0.001) 1 year later. The team members had a statistically significant improvement in their ability to articulate the medication reconciliation process. Satisfaction improved significantly for physicians, but MAs did not experience a statistically significant change. CONCLUSION: A team-based care approach to medication reconciliation was successfully implemented and sustained at 4 family medicine clinics. There was significant improvement in physician-documented medication reconciliation. Future studies need to address whether this process improves medication-list discrepancies, completeness, and accuracy.

Association of Life's Simple 7 with reduced clinically manifest abdominal aortic aneurysm: The ARIC study.

To optimize cardiovascular health, the American Heart Association (AHA) has recommended 'Life's Simple 7 (LS7)'. We tested the hypothesis that greater adherence to the LS7 cardiovascular risk metric is associated with reduced risk of developing abdominal aortic aneurysm (AAA). A total of 14,375 black and white participants aged 45-64 years at the baseline visit of the Atherosclerosis Risk in Communities (ARIC) study cohort were included in this analysis. A 14-point summary score for LS7 was calculated, and participants were classified as having poor (0-4), average (5-9), or ideal (10-14) cardiovascular health. We also counted the number of ideal components. Poisson regression was used to calculate incidence rates for AAA, and Cox regression to calculate hazard ratios adjusted for age, race, sex, and socioeconomic status. Over 25 years of follow-up, we identified 545 clinically manifest AAA events. Incident rates per 1000 person-years declined markedly across LS7 categories: 3.4 for the 'poor' category, 2.2 for 'average', and 0.9 for 'ideal'. Compared to individuals in the 'poor' LS7 category, individuals in the 'average' category had a 52% lower AAA risk (95% CI: 37% to 63%) and those in the 'ideal' category had an 80% lower risk (95% CI: 72% to 86%). For every additional ideal component, there was a 28% lower risk of AAA (95% CI: 23% to 33%). Greater adherence to the AHA's LS7 cardiovascular risk metric is associated with a reduced risk of clinically manifest AAA. These findings support the recommendation to follow LS7 for primary prevention of AAA.

Association of Left Atrial Function With Incident Chronic Kidney Disease in Older Adults.

Objective: To examine the association of left atrial (LA) function with incident chronic kidney disease (CKD) and assess the clinical utility of adding LA function to a CKD risk prediction equation. Patients and Methods: We included 4002 Atherosclerosis Risk in Communities study participants without prevalent CKD (mean ± SD age, 75±5 years; 58% female, 18% Black). Left atrial function (reservoir, conduit, and contractile strain) was evaluated by 2D-echocardiograms on 2011 to 2013. Chronic kidney disease was defined as greater than 25% decline in estimated glomerular filtration rate of less than 60 mL/min/1.73 m2, end-stage kidney disease, or hospital records. Cox proportional hazards models were used. Risk prediction and decision curve analyses evaluated 5-year CKD risk by diabetes status. Results: Median follow-up was 7.2 years, and 598 participants developed incident CKD. Incidence rate for CKD was 2.29 per 100 person-years. After multivariable adjustments, the lowest quintile of LA reservoir, conduit, and contractile strain (vs highest quintile) had a higher risk of CKD (hazard ratios [95% CIs]: 1.94 [1.42-2.64], 1.62 [1.19-2.20], and 1.49 [1.12-1.99]). Adding LA reservoir strain to the CKD risk prediction equation variables increased the C-index by 0.026 (95% CI: 0.005-0.051) and 0.031 (95% CI: 0.006-0.058) in participants without and with diabetes, respectively. Decision curve analysis found the model with LA reservoir strain had a higher net benefit than the model with CKD risk prediction equation variables alone. Conclusion: Lower LA function is independently associated with incident CKD. Adding LA function to the CKD risk prediction enhances prediction and yields a higher clinical net benefit. These findings suggest that impaired LA function may be a novel risk factor for CKD.

Hypoxia inducible factor-prolyl hydroxylase inhibitors in anemic patients with non-dialysis dependent chronic kidney disease: a meta-analysis of randomized clinical trials.

PURPOSE: Anemia persists as a challenge in chronic kidney disease (CKD) patients. Current therapies are the injectable erythropoietin stimulating agents (ESA). Concerns have been raised regarding ESA cardiovascular safety, therefore search for an alternative, convenient and safe therapy is underway. Hypoxia inducible factors-prolyl hydroxylase inhibitors (HIF-PHI) are oral agents with promising results. Numerous small studies reported favorable effects with lack of large, powered studies. METHODS: We conducted a meta-analysis of randomized clinical trials to assess the efficacy and safety of HIF-PHI in non-dialysis-dependent CKD patients. Primary outcome was hemoglobin (Hb) concentration post intervention. Secondary outcomes were all-cause mortality, MACE, and changes in iron metabolism (ferritin, hepcidin). We reported total and serious adverse effects. Data were pooled using a random effect model via RevMan 5.4 software. RESULTS: We identified 7 trials comprising of 8228 patients (mean age 66.5 ± 13.2 years, 42% were females, 53% used iron replacement) with a mean follow-up of 52 weeks. Compared with the standard of care (ESA), HIF-PHI were non-inferior for treatment of anemia, with comparable effect on mortality and major adverse cardiovascular events. HIF-PHI showed no major safety concerns. Main side effect of HIF-PHI was diarrhea. CONCLUSION: HIF-PHI might represent a safe, and convenient alternative to ESA in non-dialysis dependent CKD patients with anemia.

Retrospective analyses of factors influencing arrhythmias and the impact of arrhythmias on inpatient outcomes among hospitalized patients with hemochromatosis.

BACKGROUND: Though hemochromatosis is described as an infiltrative cardiomyopathy that can result in arrhythmias, studies are lacking on the impact of arrhythmias in this population. We examined the prevalence, factors influencing arrhythmias, and impact of arrhythmias on inpatient outcomes among hospitalized patients with hemochromatosis. METHODS: Retrospective cohort analyses were conducted using data from the National Inpatient Sample (NIS) collected between 2016 and 2018. Descriptive analyses were done to assess the prevalence of arrhythmias in patients with hemochromatosis. Univariate and multivariable logistic and linear regression models were used to examine the factors associated with arrhythmias and hospital-associated outcomes among patients with hemochromatosis. RESULTS: 11.7% of hemochromatosis patients were diagnosed with arrhythmias. Compared to hemochromatosis patients less than 40 years old, those between 40 and 59 years had 2.3 times higher odds (Adjusted Odds Ratio (AOR): 2.35; 95% Confidence Interval (CI): 1.81-3.05) of having arrhythmias relative to no arrhythmias while patients aged 60 and above had 5 times higher odds (AOR: 4.96; 95% CI: 3.74-6.58) of arrhythmias. Compared to male patients, females were significantly less likely to be diagnosed with arrhythmias. Hispanics were 36% (AOR: 0.64; 95% CI: 0.47-0.86) less likely to have arrhythmias when compared to their non-Hispanic white counterparts. Other factors associated with arrhythmias were income, insurance type, and patient disposition. Furthermore, arrhythmias were related to higher hospital mortality, longer hospital stays, and total hospital charges. CONCLUSION: Our findings accentuate the need for close monitoring and early detection of arrhythmias in patients with hemochromatosis to improve their health outcomes. Patients need to be continually educated on their medical diagnoses and the need for treatment adherence, while hospitalist physicians need to ensure good continuity of care between the hospital and primary care setting to drive hospital costs down while keeping patients healthy.

Burden of arrhythmias and predictors of mortality among multiple myeloma patients with arrhythmias.

Arrhythmias are a major cardiac complication reported among patients with multiple myeloma (MM), but these have not been further characterized in this population. We explored the prevalence of arrhythmias and examined the predictors of mortality among patients with MM with arrhythmias. The National Inpatient Sample data collected between 2016 and 2018 were used to conduct retrospective analyses. Multivariable logistic regression analyses were done to examine the predictors of mortality among patients with MM with arrhythmias. 16.9% of patients with MM reported a diagnosis of any arrhythmias and 70.7% of these were atrial fibrillation. Patients aged 70 years and above had 21% lower odds (adjusted OR (AOR): 0.79; 95% CI: 0.68 to 0.92) of inpatient mortality relative to younger patients. Those in the non-Hispanic black, Hispanic, and non-Hispanic other category were 1.38 (95% CI: 1.16 to 1.64), 1.53 (95% CI: 1.19 to 1.97), and 1.69 (95% CI: 1.29 to 2.21) times more likely to die during hospitalization compared with their counterparts who were non-Hispanic whites. Relative to patients with MM who were on Medicare, those on private (AOR: 1.28; 95% CI: 1.06 to 1.54) and other insurance types (AOR: 1.78; 95% CI: 1.23 to 2.58) had higher odds of mortality. Other predictors of inpatient mortality were elective admission (AOR: 0.67; 95% CI: 0.52 to 0.85) and Charlson comorbidity indices between 5-7 (AOR: 1.23; 95% CI: 1.07 to 1.41) and ≥8 (AOR: 1.45; 95% CI: 1.21 to 1.73) compared with comorbidity indices between 0 and 4. Our study adds to the body of knowledge on the need for proper diagnosis and management of cardiac arrhythmias in patients with MM. Research is needed to further assess the time of arrhythmia diagnosis and its impact on health outcomes among patients with MM.

Neonatal Jaundice: Knowledge and Practices of Healthcare Providers and Trainees in Southwest Nigeria.

Severe neonatal jaundice (SNNJ) is a leading cause of neonatal morbidity and mortality in low- and middle-income countries (LMICs). Risk mitigation and management modalities for SNNJ have led to marked reduction in complications in high-income countries but not in LMICs likely in part due to knowledge gaps among healthcare providers. This study, a cross-sectional study conducted in Ogbomosho, Nigeria, aimed to identify SNNJ knowledge and practices among Nigerian healthcare providers/trainees. Healthcare providers/trainees completed a structured questionnaire. Healthcare providers/trainees included are nurse midwives (33.4%), nurses (18.6%), nursing students (15.2%), traditional birth attendants (TBAs) (12.7%), physicians (10.2%), and medical students (9.9%). Most physicians were aware of the common causes of SNNJ; however, knowledge deficits in other groups were notable. Despite most providers endorsing that glucose-6-phosphate dehydrogenase deficiency can cause SNNJ (91% of physicians, 60% of nurses, 71% of midwives, 81% of medical students, 43% of nursing students, 7% of TBAs), very few providers recognized that it is common, ranging from 3% in nurses up to a high of 47% among medical students. Gaps in provider knowledge regarding preventative measures and sequela were also noted. These data identified significant knowledge gaps regarding the etiology of SNNJ among healthcare providers/trainees, which can lead to missed opportunities in effective prevention and treatment. These deficits must be addressed if we are to eliminate tragic and preventable complications from SNNJ in Nigeria and other LMICs.

New Onset Non-Convulsive Status Epilepticus Despite Cefepime Renal Dose Adjustment.

Cefepime, a widely used fourth-generation cephalosporin for coverage of both gram-positive and gram-negative bacteria, has been reported to have associated neurological adverse effects. These effects have been seen mostly in patients mostly with impaired renal function, and currently, dosing is based on creatinine clearance to reduce its toxic effect profile. Despite renal dose adjustment, we present a case of a 40-year-old woman who was managed for Escherichia coli bacteremia, acute kidney injury, and hemorrhagic shock. About 96 hours after cefepime therapy was commenced, she was noted to be twitching with passive movement of her upper limb and myoclonus of the facial muscles. Her workup including computed tomography (CT) scan of the head and magnetic resonance imaging (MRI) brain were negative. Electroencephalograph (EEG) showed 2 Hertz sharply contoured triphasic form rhythmic waves suggestive of nonconvulsive status epilepticus (NCSE). She received antiseizure medications and later had hemodialysis for effective clearance of cefepime. She had significant improvement in her neurological status following hemodialysis and a repeat EEG showed no further seizure activity. Clinicians should be aware of the risk of NCSE in patients on cefepime despite renal dose adjustment. Once identified, immediate discontinuation of the offending drug, treatment with benzodiazepines, and clearance of the medication with hemodialysis is recommended.

A Difference-in-Difference Study Evaluating the Effect of Minimum Wage Policy on Body Mass Index and Related Health Behaviors.

Minimum wage laws are a promising policy lever to promote health equity, but few rigorous evaluations have tested whether and how minimum wage policy affects health outcomes. This paper describes an ongoing difference-in-difference study evaluating the health effects of the 2017 Minneapolis Minimum Wage Ordinance, which incrementally increases the minimum wage to $15/hr. We present: (1) the conceptual model guiding the study including mediating mechanisms, (2) the study design, and (3) baseline findings from the study, and (4) the analytic plan for the remainder of the study. This prospective study follows a cohort of 974 low-wage workers over four years to compare outcomes among low-wage workers in Minneapolis, Minnesota, and those in a comparison city (Raleigh, North Carolina). Measures include height/weight, employment paystubs, two weeks of food purchase receipts, and a survey capturing data on participant demographics, health behaviors, and household finances. Baseline findings offer a profile of individuals likely to be affected by minimum wage laws. While the study is ongoing, the movement to increase local and state minimum wage is currently high on the policy agenda; evidence is needed to determine what role, if any, such policies play in improving the health of those affected.

Efficacy and safety of dual intravenous artesunate plus quinine compared to intravenous artesunate for cerebral malaria in a triple blinded parallel multisite randomized controlled trial in Nigerian children: DUAL PAQ TRIAL Protocol.

BACKGROUND: Evidence exists as to the criticality of the first 24 h in the management of cerebral malaria. The morbidity and the mortality rate (35%) with the current intravenous monotherapy for the initial treatment of cerebral malaria are unacceptably high. Combination therapy and a shorter course of effective medication have been shown to improve outcomes in human participants in the treatment of other diseases. This study outlines a protocol to conduct a triple blinded parallel randomized controlled trial on cerebral malaria using dual intravenous medications compared to the current standard of monotherapy. METHODS: This is a parallel multi-site randomized controlled superiority triple blinded trial consisting of intravenous artesunate plus quinine and a control arm of intravenous artesunate only. Eligible and assenting children aged 6 months to 17 years will be recruited from 4 tertiary hospitals by random selection from the list of tertiary hospitals in Nigeria. Participants will be randomized and assigned in parallel into two arms using random numbers generated from GraphPad Prism (version 9) by a clinical pharmacologist who has no link with the investigators, the patients, or the statistician. The primary measurable outcome is survival at 12, 24, and 48 h post-randomization. A composite secondary outcome consists of the number of children that regained consciousness, parasitaemia and defervescence at 12 and 24 h post-randomization and haematological and inflammatory markers at 24 and 48 h post-randomization. Adverse events both solicited and unsolicited are recorded all through the study post-randomization. The study is approved by the State Research Ethics Review Committee. Data analysis will be performed in GraphPad Prism version 9. DISCUSSION: The outcome of this analysis will give insight into the efficacy and safety of dual intravenous antimalaria in the treatment of cerebral malaria among Nigerian children compared with the standard of care. The safety profile of this intervention will also be highlighted. This may help inform physicians on the optimal treatment for cerebral malaria to improve outcomes and reduce recrudescence and treatment failure. TRIAL REGISTRATION: Pan Africa Clinical Trial Registry PACTR202102893629864 . 23/02/2021.

Education and Attitudes on Medical Cannabis in Family Medicine Residency Programs.

BACKGROUND AND OBJECTIVES: Medical cannabis has become increasingly prevalent in the United States, however the extent of family medicine resident education on this topic remains unknown. The objective of this study was to ascertain the current state of medical cannabis education across this population and identify patterns in education based on state legality and program director (PD) practices. METHODS: Survey questions were part of the Council of Academic Family Medicine Educational Research Alliance (CERA) omnibus survey from May 2019 to July 2019. PDs from all Accreditation Council for Graduate Medical Education (ACGME)-accredited US family medicine residency programs received survey invitations by email. RESULTS: A total of 251 (40.7%) PDs responded, with 209 (83.6% [209/250]) reporting at least 1 hour of didactic curriculum regarding cannabis. The most common context was substance misuse (mean 3.0±4.1 hours per 3 years), followed by pain management (2.7±3.4 hours), and management of other conditions (2.1±2.7 hours). Thirty-eight programs (15.2% [38/250]) offered clinical experiences related to medical cannabis, and PDs who had previously prescribed or recommended medical cannabis were more likely to offer this experience (P<.0001). Experiences peaked after 3 to 5 years of medical cannabis legality. PD confidence in resident counseling skills was low overall, but did increase among programs with clinical experiences (P=.0033). CONCLUSIONS: The current trajectory of medical cannabis use in the United States makes it likely that residents will care for patients interested in medical cannabis, therefore it is important residents be prepared to address this reality. Opportunities exist for improving medical cannabis education in family medicine residency programs.

Plasma Galectin-3 and Sonographic Measures of Carotid Atherosclerosis in the Atherosclerosis Risk in Communities Study.

Galectin-3 is a ß-galactoside-binding lectin that plays a role in the regulation of several conditions that are associated with atherosclerosis. The goal of this cross-sectional study was to assess the association of plasma galectin-3 concentrations with sonographic measures of carotid atherosclerosis in the Atherosclerosis Risk in Communities study. Linear regression was used to determine the difference and 95% confidence intervals (CIs) for carotid intima-media thickness (cIMT) by categorical and continuous representations of galectin-3. Logistic regression was used to determine the odds ratio and 95% CI, separately, for dichotomized cIMT (75th percentile = 0.9 mm) and carotid plaque and/or shadowing. Compared to those in the first quintile of galectin-3, those in the fifth quintile of galectin-3 level had higher cIMT (mean difference: 0.020 mm after multivariable adjustment; P trend = .04). Moreover, compared to those in the lowest galectin-3 quintile, those in the highest galectin-3 quintile had higher odds of carotid plaque/and or shadowing (odds ratio 1.13 after multivariable adjustment; P trend = .014). Higher levels of galectin-3 are associated with greater carotid atherosclerosis. Our findings provide support for the role of inflammatory biomarkers in the pathogenesis of atherosclerosis and suggest galectin-3 as a possible target for intervention in the prevention or management of atherosclerotic disease.

Greater Adherence to Life's Simple 7 Is Associated With Less Arterial Stiffness: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Greater arterial stiffness is associated independently with increased cardiovascular disease risk. The American Heart Association (AHA) has recommended following "Life's Simple 7 (LS7)" to optimize cardiovascular health; we tested whether better LS7 in middle age is associated with less arterial stiffness in later life. METHODS: We studied 4,232 black and white participants aged 45-64 years at the baseline (1987-89) visit of the Atherosclerosis Risk in Communities Study cohort who also had arterial stiffness measured in 2011-13 (mean ± SD interval: 23.6 ± 1.0 years). We calculated a 14-point summary score for baseline LS7 and classified participants as having "poor" (0-4), "average" (5-9), or "ideal" (10-14) cardiovascular health. We used logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (95% CI) for arterial stiffening: a high carotid-femoral pulse wave velocity (cfPWV, ≥13.23 m/s) or a high central pulse pressure (central PP, ≥ 82.35 mm Hg). RESULTS: The age, race, sex, and heart rate-adjusted ORs (95% CI) for high cfPWV in the "ideal," "average," and "poor" LS7 summary categories were 1 (Reference), 1.30 (1.11, 1.53), and 1.68 (1.10,2.56), respectively (P-trend = 0.0003). Similarly, the adjusted ORs (95% CI) for high central PP across LS7 summary categories were 1 (Reference), 1.48 (1.27, 1.74), and 1.63 (1.04, 2.56), respectively (P-trend <0.0001). CONCLUSION: Greater LS7 score in middle age is associated with less arterial stiffness 2-3 decades later. These findings further support the AHA recommendation to follow LS7 for cardiovascular disease prevention.

GlycA, a Novel Inflammatory Marker and Its Association With Peripheral Arterial Disease and Carotid Plaque: The Multi-Ethnic Study of Atherosclerosis.

GlycA, a composite biomarker of systemic inflammation, is associated with cardiovascular disease (CVD) and mortality, but its relationship with peripheral artery disease (PAD) is unknown. We assessed whether plasma GlycA is associated with ankle-brachial index (ABI), carotid plaque (CP), and incident clinical PAD among 6466 Multi-Ethnic Study of Atherosclerosis participants without CVD at baseline. GlycA, ABI, and CP were measured at baseline. Both ABI and CP were remeasured at 10 years. Incident clinical PAD was ascertained from hospital records. We used logistic, Cox, and linear mixed regression models adjusted for demographic and lifestyle factors. Mean (standard deviation, SD) was 62 (10) years for age and 381 (61) µmol/L for GlycA; 53% were women. GlycA was associated with both prevalent low ABI ≤0.8 (prevalence odds ratio [95% confidence interval, CI] per SD increment in GlycA, 1.65 [1.39-1.97]) and CP (1.19 [1.11-1.27]) at baseline. There were no significant associations of GlycA with incident low ABI, incident CP, or 10-year change in ABI or CP score. We identified 110 incident cases of PAD after 79 590 person-years. The hazard ratio (95% CI) of incident PAD per SD increment in GlycA was 1.38 (1.14-1.66). In conclusion, GlycA was associated with prevalent low ABI, prevalent CP, and incident PAD after a median of 14 years.

Association of monocyte myeloperoxidase with incident cardiovascular disease: The Atherosclerosis Risk in Communities Study.

Myeloperoxidase (MPO) is a heme-containing peroxidase found in azurophilic granules of neutrophils and monocytes. Epidemiological studies have reported greater plasma MPO concentration to be associated with increased incidence of several cardiovascular diseases (CVD), but the association of intracellular monocyte MPO (mMPO) with CVD is unclear. The prospective population-based Atherosclerosis Risk in Communities (ARIC) cohort study measured mMPO using flow cytometry in 1,465 participants. The association of mMPO with incident cardiovascular disease (CVD, comprising incident coronary heart disease (CHD), heart failure, stroke, peripheral artery disease, and cardiovascular mortality) was examined over a median 9.6 years of follow-up (n = 290 CVD events). There was no statistically significant association between mMPO and all incident CVD events in either age, sex, and race-adjusted proportional hazards models (HR (95% CI) across tertiles of mMPO: 1, 1.09 (0.76, 1.57), and 0.78 (0.52, 1.15), P-trend = 0.21) or adjusted for other major CVD risk factors (HR (95% CI): 1, 1.17 (0.81, 1.69), and 0.87 (0.58, 1.29), P-trend = 0.50). There also was no association between mMPO tertiles and incident CHD, heart failure, or all-cause mortality, examined separately. In conclusion, intracellular monocyte myeloperoxidase was not associated with incident cardiovascular disease in this prospective population-based study.

Galectin-3 and the incidence of abdominal aortic aneurysm: the atherosclerosis risk in communities (ARIC) study.

Galectin-3, a ß-galactosidase binding lectin, known to be involved in inflammatory processes may be associated with abdominal aortic aneurysm (AAA) incidence. We examined the prospective association between plasma galectin-3 and incident AAA in 9,704 participants of the Atherosclerosis Risk in Communities (ARIC) study cohort. We followed participants from 1996-1998 through 2011 (124,260 person-years) for incident AAA (n=325) defined by ICD codes from hospital records and death certificates. At baseline, participants had a mean (SD) age of 62.8 (5.7) years; 20.9% were blacks and 56.5% females. The median (25th-75th percentile) galectin-3 level was 14.2 (12.0-16.9) ng/mL. Galectin-3 was correlated positively with most cardiovascular risk factors and with several cardiac or inflammatory biomarkers (C-reactive protein, troponin-T, and NT-proBNP). Using Cox proportional hazards regression adjusted for demographic variables and measured AAA risk factors, the hazard ratios for AAA across galectin-3 quintiles were 1 (Referent), 1.54 (1.05-2.26), 1.58 (1.05-2.41), 1.76 (1.15-2.72), and 1.92 (1.22-3.01) (p for trend =0.01). Further adjustment for the cardiac and inflammatory biomarkers largely attenuated the association between galectin-3 and AAA [AAA hazard ratio for galectin-3 Quintile 5 vs. Quintile 1: 1.29 (0.81-2.05); p-trend across quintiles =0.44]. In conclusion, higher concentrations of plasma galectin-3 were associated with greater incidence of AAA though not independent of other cardiac and inflammatory biomarkers. This reinforces that galectin-3, a systemic biomarker reflecting inflammation and probably increased systemic vascular resistance, is elevated early in the pathogenesis of AAA.