Elevated Cardiac Biomarkers in Relatively Healthy U.S. Adults.

Background: Despite the importance of early cardiovascular disease (CVD) intervention, little data exists for evaluating cardiovascular risk in adults without traditional CVD risk factors (e.g., diabetes, hypertension). Methods: We included 4,544 adults from the 1999-2004 National Health and Nutrition Examination Survey without prevalent diabetes, hypertension, chronic kidney disease, or CVD. We used multi-variable adjusted Cox proportional hazards regression modeling to assess the relationship between logarithmically transformed cardiac biomarkers (high sensitivity cardiac troponin T (hs-cTnT), hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP) and CVD mortality among a nationally representative cohort of relatively healthy adults. Results: The mean age was 38.2 years (SD 12.8) and 53.9% were women. 8.7% had elevated levels of hs-cTnT or NT-proBNP above previously established thresholds for subclinical CVD. In multivariable adjusted models, each doubling of hs-cTnT was associated with a 49% increased risk of CVD mortality (Hazard Ratio (HR) 1.49, 95%CI 1.02-2.17, p=0.04). Only two of the hs-cTnI assays (Abbott and Ortho) were significantly associated with CVD mortality (Abbott HR 1.48, 95%CI 1.06-2.07, p=0.02; Ortho HR 1.47, 95%CI 1.23-1.77, p=0.0001). Each doubling of NT-proBNP was associated with a 41% increased risk of CVD mortality (HR 1.38, 95%CI 1.09-1.74, p=0.008). Conclusion: Younger patients who maintain relatively good health may still carry occult CVD risk. Efforts to reduce population-wide CVD should consider novel methods for risk stratification, as standard CVD risk factors may overlook subpopulations at risk.

Cardiovascular-kidney-metabolic syndrome: A step toward multidisciplinary and inclusive care.

In a recent Presidential Advisory report, the American Heart Association (AHA) defined cardiovascular-kidney-metabolic (CKM) syndrome as a spectrum of pathology associated with dysfunctional or excess adiposity and leading to adverse cardiovascular outcomes. Implementing the guidelines set forth by the AHA has the potential to improve population-wide CKM health.

Estimating kidney function in patients with cancer: A narrative review.

AIM: Accurate evaluation of glomerular filtration rate (GFR) is crucial in Oncology as drug eligibility and dosing depend on estimates of GFR. However, there are no clear guidelines on the optimal method of determining kidney function in patients with cancer. We aimed to summarize the evidence on estimation of kidney function in patients with cancer. METHODS: We searched PubMed for literature discussing the performance of GFR estimating equations in patients with malignancy to create a table of the evidence for creatinine- and cystatin c-based equations. We further reviewed novel estimation techniques such as panel eGFR, real-time measured GFR, and functional magnetic resonance imaging. RESULTS: The commonly used GFR estimating equations were derived from populations of patients without cancer. These equations may be less applicable in Oncology due to severe sarcopenia, inflammation, and other physiologic changes in patients with cancer. The Cockcroft-Gault equation currently dominates in clinical Oncology despite significant limitations and accumulating evidence for use of the CKD-EPICr formula. Additional considerations in the practice of Oncology include a recently developed equation (CamGFRv2, also called the Janowitz formula) and the use of cystatin c-based equations to overcome some of the barriers to accurate GFR estimation based on creatinine alone. CONCLUSION: Overall, we suggest using the CKD-EPI equations (either cystatin c or creatinine-based) among patients with cancer in routine clinical practice and measured GFR for patients at a critical threshold for treatment decisions.

Review article: Practical considerations for fluid resuscitation in cirrhosis.

BACKGROUND: Standard clinical methods of assessing volume and providing resuscitation are not always applicable to patients with advanced or decompensated cirrhosis. Despite this being well known from a clinical perspective, there remains relatively little evidence to guide clinicians though fluid management in patients with cirrhosis and, often, multi-organ system dysfunction. AIMS: This review summarises the current understanding of the circulatory dysfunction in cirrhosis, modalities for assessing volume status, and considerations for fluid selection. It additionally provides a practical approach to fluid resuscitation. METHODS: We review current literature on cirrhosis pathophysiology in steady-state and shock, clinical implications of fluid resuscitation, and strategies to assess intravascular volume. Literature reviewed here was identified by the authors through PubMed search and review of selected papers' references. RESULTS: Clinical management of resuscitation in advanced cirrhosis remains relatively stagnant. Although several trials have attempted to establish the superior resuscitative fluid, the lack of improvement in hard clinical outcomes leaves clinicians without clear guidance. CONCLUSIONS: The absence of consistent evidence for fluid resuscitation in patients with cirrhosis limits our ability to produce a clearly evidence-based protocol for fluid resuscitation in cirrhosis. However, we propose a preliminary practical guide to managing fluid resuscitation in patients with decompensated cirrhosis. Further studies are needed to develop and validate volume assessment tools in the specific context of cirrhosis, while randomised clinical trials of protocolized resuscitation may improve care of this patient population.

Structured handoff to improve communication from inpatient to outpatient dialysis units: A quality improvement project.

BACKGROUND: Patients with end-stage kidney disease requiring dialysis encounter high hospital readmission rates. One contributor is poor communication between hospitals and outpatient dialysis facilities. We hypothesized that improved communication may reduce 30-day hospital readmissions for patients on dialysis at an urban, safety net hospital. METHODS: We created a standardized discharge handoff tool that is easy to use and provides concise data for dialysis centers. The handoff tool is a novel, electronic MACRO template (called a "dot-phrase") to be included in discharge documentation. Instructions for the dot-phrase and electronic facsimile (e-faxing) were sent to Internal Medicine residents immediately prior to their rotation on an inpatient Renal service. We then measured the intervention implementation rate and its impact on hospital readmission metrics. RESULTS: We compared 3 months of preintervention and 6 months of postintervention data, identifying 82 and 135 index discharges in each respective study period. Patients were predominantly male (56.2%) and receiving hemodialysis (89.8%); a minority (9.2%) were undomiciled at the time of discharge. Mean age was 60.5 years (SD 14.0). Renal discharges followed by 30-day Renal readmission were not statistically lower in the postintervention group for the index discharge alone (26.8% vs. 20.0%, p = 0.12), but were for overall discharges (51.2% vs. 25.7%, p < 0.0001). The dot-phrase was used in 95.4% of discharge summaries, and 74.7% of discharge summaries were e-faxed within 24 h of discharge. CONCLUSION: There was high uptake of a standardized discharge handoff tool among Internal Medicine residents on a Renal inpatient service. Using a handoff tool and e-faxing may improve communication with outpatient dialysis centers and may reduce readmissions among some patients but is likely insufficient to fully address high readmission rates. Subsequent intervention iterations would benefit from further collaboration with outpatient dialysis units for customization of the handoff tool to meet local communication needs.

Severe hyponatremia due to surreptitious water intoxication in a hospitalized patient.

Hyponatremia is a common electrolyte abnormality among hospitalized patients and often present as first sign of other underlying medical conditions. Severe hyponatremia can be life threatening and requires prompt diagnosis and treatment. We present a case of refractory hyponatremia that was a diagnostic challenge requiring a prolonged hospitalization. Diagnosis of primary polydipsia was ultimately suspected due to improbable 24-h urine studies and confirmed through complete removal of free water access in the form of disconnecting the bathroom faucet in the patient's hospital room. Diagnosis and management of primary polydipsia is further discussed.

Association of cardiac biomarkers, kidney function, and mortality among adults with chronic kidney disease.

Background and Aims: The performance of high sensitivity troponin T (hs-cTnT), hs-cTnI, and N-terminal pro-hormone brain natriuretic peptide (NT-proBNP) in patients with chronic kidney disease (CKD) is poorly understood. Methods: We included adults with CKD (eGFR<60 ml/min/1.73m2) in the 1999-2004 NHANES. We calculated the 99th percentile of hs-cTnT, hs-cTnI (Abbott, Ortho, and Siemens assays), and NT-proBNP, measured the association between eGFR and cardiac biomarker concentration, and used Cox regression models to assess the relationship between cardiac biomarkers and CVD mortality. Results: Across 1,068 adults with CKD, the mean [SD] age was 71.9[12.7] years and 61.2% were female; 78.8% had elevated NT-proBNP and 42.6% had elevated hs-cTnT based on traditional clinical reference limits. The 99th percentile of hs-cTnT was 122 ng/L (95% confidence interval (CI) 101-143), hs-cTnIAbbott was 69 ng/L (95% CI 38-99), and NT-proBNP was 8952 pg/mL (95% CI 7506-10,399). A 10 ml/min decrease in eGFR was associated with greater increases in hs-cTnT and NT-proBNP than hs-cTnI (hs-cTnT: 27.5% increase (ß=27.5, 95% CI 28.2-43.3)), NT-proBNP 46.0% increase (ß=46.0, 95% CI 36.0-56.8), hs-cTnISiemens 17.9% (ß=17.9, 95% CI 9.7-26.7). Each doubling of hs-cTnT, hs-cTnI, and NT-proBNP were associated with CVD mortality (hs-cTnT HR 1.62 [95% CI 1.32-1.98], p<0.0001; hs-cTnISiemens HR 1.40 [95% CI 1.26-1.55], p<0.0001; NT-proBNP HR 1.29 [95% CI 1.19-1.41], p<0.0001). Conclusions and Relevance: Community dwelling adults with CKD have elevated concentrations of cardiac biomarkers, above established reference ranges. Of the troponin assays, hs-cTnI concentration appears to be most stable across eGFR categories and is associated with CVD mortality.

The relationship between low levels of albuminuria and cardiovascular mortality among apparently healthy adults.

Background: Albuminuria is associated with cardiovascular events among adults with underlying cardiovascular disease and diabetes, even at low levels of urinary albumin excretion. We hypothesized that low levels of albuminuria in the 'normal' range (urinary albumin-to-creatine ratio (UACR) <30 mg/g) are associated with cardiovascular death among apparently healthy adults. Methods: We studied adults who participated in the 1999-2014 National Health and Nutrition Examination Survey. We excluded participants with baseline cardiovascular disease, hypertension, diabetes, estimated glomerular filtration rate (eGFR) <60ml/min/1.73m2, those who were currently pregnant, and those who had received dialysis in the last year. After excluding these conditions, only 5.0% of the remaining population had UACR ≥30 mg/g (N=873) and were excluded. The final sample size was 16,247. We assessed the relationship between UACR and cardiovascular and all-cause mortality using multivariable-adjusted Cox proportional hazards models. Models were adjusted for age, sex, race or ethnicity, smoking status, systolic blood pressure, hemoglobin A1c, total cholesterol, health insurance, food insecurity, serum albumin, body mass index, use of statins, and eGFR. Results: Mean age was 38.9 years (SD 13.6) and 53.7% were women. The median length of follow-up was 12.2 years. In multivariable-adjusted models, each doubling of UACR (within the <30 mg/g range) was associated with a 36% higher risk of cardiovascular death [HR 1.36 (95% confidence interval (CI) 1.11-1.65)] and a 28% higher risk of all-cause mortality [HR 1.28 (95%CI 1.17-1.41)]. The highest tertile of UACR (7.1-29.9 mg/g) was associated with an 87% higher risk of cardiovascular death [HR 1.87 (95%CI 1.20-2.92)] and 59% higher risk of all-cause mortality [HR 1.59 (95%CI 1.28-1.96)], compared with the lowest tertile (< 4.3 mg/g). Conclusions: In a nationally representative sample of relatively healthy community-dwelling adults, higher levels of albuminuria in the conventionally "normal" range <30 mg/g in healthy individuals are associated with greater mortality. Overall, our findings contribute to the growing body of evidence on the existence of a risk gradient across all levels of albuminuria, even in the so-called normal range.

Use of a focus group-based cognitive interview methodology to validate a cooking behavior survey among African-American adults.

Disparities in diet-related diseases persist among African-Americans despite advances in risk factor identification and evidence-based management strategies. Cooking is a dietary behavior linked to improved dietary quality and cardiometabolic health outcomes. However, epidemiologic studies suggest that African-American adults report a lower frequency of cooking at home when compared to other racial groups, despite reporting on average cooking time. To better understand cooking behavior among African-Americans and reported disparities in behavior, we sought to develop a survey instrument using focus group-based cognitive interviews, a pretesting method that provides insights into a survey respondent's interpretation and mental processing of survey questions. A comprised survey instrument was developed based on input from a community advisory board, a literature review, and a content review by cooking behavior experts. The cognitive interview pretesting of the instrument involved African-American adults (n = 11) at risk for cardiovascular disease who were recruited from a community-based participatory research study in Washington, D.C., to participate in a focus group-based cognitive interview. Cognitive interview methodologies included the verbal think-aloud protocol and the use of retrospective probes. Thematic analysis and evaluation of verbalized cognitive processes were conducted using verbatim transcripts. Five thematic themes related to the survey were generated: (1) Clarity and relevancy of question items; (2) influence of participants' perspectives and gender roles; (3) participant social desirability response to questions; (4) concern regarding question intent. Eleven survey items were determined as difficult by participants. Cooking topics for these items were: cooking practices, cooking skills, cooking perception (how one defines cooking), food shopping skills, and socialization around cooking. Question comprehension and interpreting response selections were the most common problems identified. Cognitive interviews are useful for cooking research as they can evaluate survey questions to determine if the meaning of the question as intended by the researcher is communicated to the respondents-specific implications from the results that apply to cooking research include revising questions on cooking practice and skills. Focus-group-based cognitive interviews may provide a feasible method to develop culturally grounded survey instruments to help understand disparities in behavior for culturally relevant diet behaviors such as cooking.

Associations between neighborhood socioeconomic deprivation and severity of depression: Data from the National Health and Nutrition Examination Survey, 2011-2014.

Neighborhood socioeconomic disadvantage may contribute to depression. This study examined associations between neighborhood socioeconomic disadvantage, measured as deprivation, and depression severity within a broadly representative sample of the U.S. adult population. The sample (n = 6308 U.S. adults) was from the 2011-2014 National Health and Nutrition Examination Survey. Neighborhood deprivation was calculated using the 2010 U.S. Census and shown in tertile form. Depression severity was calculated from responses to the Patient Health Questionnaire-9 (PHQ-9) as a continuous depression severity score and binary Clinically Relevant Depression (CRD). Multilevel modeling estimated the relationship between deprivation and depression (reference = low deprivation). Models were additionally stratified by gender and race/ethnicity. U.S. adults living in high deprivation neighborhoods were more likely to have a higher PHQ-9 score (p < 0.0001). In unadjusted models, living in high deprivation neighborhoods associated with higher PHQ-9 (ß = 0.89, SE = 0.15, p < 0.0001) and higher odds of CRD (OR = 1.35, 95% CI = 1.20-1.51). Living in medium deprivation neighborhoods associated with higher PHQ-9 (ß = 0.49, SE = 0.16, p = 0.0019). Associations between deprivation and depression severity lost significance after adjusting for individual-level SES. The results suggest that, for U.S. adults, the relationship between neighborhood-level disadvantage and depression may be attenuated by individual-level SES.

LDL associates with pro-inflammatory monocyte subset differentiation and increases in chemokine receptor profile expression in African Americans.

BACKGROUND: In the United States, African Americans (AAs) have greater risk for Class III obesity and cardiovascular disease (CVD). Previous reports suggest that AAs have a different immune cell profile when compared to Caucasians. METHODS: The immune cell profile of AAs was characterized by flow cytometry using two experimental setups: ex vivo (N = 40) and in vitro (N = 10). For ex vivo experiments, PBMC were treated with participant serum to understand how lipid contents may contribute to monocyte phenotypic differences. For in vitro experiments, monocytes were low-density lipoprotein (LDL)- or vehicle-treated for four hours and subsequently analyzed by flow cytometry and RT-qPCR. RESULTS: When PBMCs were treated with participant sera, subsequent multivariable regression analysis revealed that serum triglycerides and LDL levels were associated with monocyte subset differences. In vitro LDL treatment of monocytes induced a phenotypic switch in monocytes away from classical monocytes accompanied by subset-specific chemokine receptor CCR2 and CCR5 expression changes. These observed changes are partially translation-dependent as determined by co-incubation with cycloheximide. CONCLUSIONS: LDL treatment of monocytes induces a change in monocyte subsets and increases CCR2/CCR5 expression in a subset-specific manner. Understanding the molecular mechanisms could prove to have CVD-related therapeutic benefits, especially in high-risk populations with hyperlipidemia and increased risk for CVD.

Chronic Stress-Related Neural Activity Associates With Subclinical Cardiovascular Disease in a Community-Based Cohort: Data From the Washington, D.C. Cardiovascular Health and Needs Assessment.

Background: Psychosocial stress correlates with cardiovascular (CV) events; however, associations between physiologic measures of stressors and CVD remain incompletely understood, especially in racial/ethnic minority populations in resource-limited neighborhoods. We examined associations between chronic stress-related neural activity, measured by amygdalar 18Fluorodeoxyglucose (18FDG) uptake, and aortic vascular FDG uptake (arterial inflammation measure) in a community-based cohort. Methods: Forty participants from the Washington, DC CV Health and Needs Assessment (DC-CHNA), a study of a predominantly African-American population in resource-limited urban areas and 25 healthy volunteers underwent detailed phenotyping, including 18FDG PET/CT for assessing amygdalar activity (AmygA), vascular FDG uptake, and hematopoietic (leukopoietic) tissue activity. Mediation analysis was used to test whether the link between AmygA and vascular FDG uptake was mediated by hematopoietic activity. Results: AmygA (1.11 ± 0.09 vs. 1.05 ± 0.09, p = 0.004) and vascular FDG uptake (1.63 ± 0.22 vs. 1.55 ± 0.17, p = 0.05) were greater in the DC-CHNA cohort compared to volunteers. Within the DC-CHNA cohort, AmygA associated with vascular FDG uptake after adjustment for Framingham score and body mass index (ß = 0.41, p = 0.015). The AmygA and aortic vascular FDG uptake relationship was in part mediated by splenic (20.2%) and bone marrow (11.8%) activity. Conclusions: AmygA, or chronic stress-related neural activity, associates with subclinical CVD risk in a community-based cohort. This may in part be mediated by the hematopoietic system. Our findings of this hypothesis-generating study are suggestive of a potential relationship between chronic stress-related neural activity and subclinical CVD in an African American community-based population. Taken together, these findings suggest a potential mechanism by which chronic psychosocial stress, such as stressors that can be experienced in adverse social conditions, promotes greater cardiovascular risk amongst resource-limited, community-based populations most impacted by cardiovascular health disparities. However, larger prospective studies examining these findings in other racially and ethnically diverse populations are necessary to confirm and extend these findings.

The Mediating role of perceived discrimination and stress in the associations between neighborhood social environment and TV Viewing among Jackson Heart Study participants.

OBJECTIVES: The aim of this study was to test the mediating role of perceived discrimination and stress on associations between perceived neighborhood social environment (PNSE) and TV viewing. METHODS: Baseline data were used for 4716 participants (mean age = 55.1 y; 63.4% female) in the Jackson Heart Study (JHS), a large prospective cohort study of African Americans in Jackson, Mississippi. One binary TV viewing outcome was created: ≥4 h/day versus <4 h/day. PNSE variables included neighborhood violence, problems (higher value = more violence/problems), and social cohesion (higher value = more cohesion). Mediators included perceived lifetime discrimination, daily discrimination, and chronic stress (higher value = greater discrimination/stress). Multivariable regression was used with bootstrap-generated 95% bias-corrected confidence intervals (BC CIs) to test for mediation adjusting for demographics, health-related and psychosocial factors, and population density. RESULTS: Neighborhood violence, problems, and social cohesion were indirectly associated with TV viewing through lifetime discrimination (OR = 1.03, 95%BC CI = 1.00, 1.07; OR = 1.03, 95%BC CI = 0.99, 1.06 [marginal]; OR = 0.98, 95%BC CI = 0.94, 0.99, respectively) and chronic stress (OR = 0.95, 95%BC CI = 0.90, 0.99; OR = 0.96, 95%BC CI = 0.92, 0.99; OR = 1.05, 95%BC CI = 1.01, 1.10, respectively). Daily discrimination was neither directly nor indirectly associated with TV viewing. CONCLUSIONS: Each PNSE variable was indirectly associated with TV viewing via lifetime discrimination and perceived stress, but not with daily discrimination among JHS participants. Unexpected directionality of mediating effects of lifetime discrimination and chronic stress should be replicated in future studies. Further research is also needed to pinpoint effective community efforts and physical environmental policies (e.g., installing bright street lights, community policing) to reduce adverse neighborhood conditions and psychosocial factors, and decrease TV viewing and subsequent cardiovascular disease risk.

Comparing Methods to Identify Wear-Time Intervals for Physical Activity With the Fitbit Charge 2.

There is no established method for processing data from commercially available physical activity trackers. This study aims to develop a standardized approach to defining valid wear time for use in future interventions and analyses. Sixteen African American women (mean age = 62.1 years and mean body mass index = 35.5 kg/m2) wore the Fitbit Charge 2 for 20 days. Method 1 defined a valid day as ≥10-hr wear time with heart rate data. Method 2 removed minutes without heart rate data, minutes with heart rate ≤ mean - 2 SDs below mean and ≤2 steps, and nighttime. Linear regression modeled steps per day per week change. Using Method 1 (n = 292 person-days), participants had 20.5 (SD = 4.3) hr wear time per day compared with 16.3 (SD = 2.2) hr using Method 2 (n = 282) (p < .0001). With Method 1, participants took 7,436 (SD = 3,543) steps per day compared with 7,298 (SD = 3,501) steps per day with Method 2 (p = .64). The proposed algorithm represents a novel approach to standardizing data generated by physical activity trackers. Future studies are needed to improve the accuracy of physical activity data sets.