A Pilot Study and Ecological Model of Smoking Cues to Inform Mobile Health Strategies for Quitting Among Low-Income Smokers.

One crucial factor that leads to disparities in smoking cessation between groups with higher and lower socioeconomic status is more prevalent socioenvironmental smoking cues in low-income communities. Little is known about how these cues influence socioeconomically disadvantaged smokers in real-world scenarios and how to design interventions, especially mobile phone-based interventions, to counteract the impacts of various types of smoking cues. We interviewed 15 current smokers living in low-income communities and scanned their neighborhoods to explore smoking-related experiences and identify multilevel cues that may trigger them to smoke. Findings suggest four major types of smoking cues influence low-income smokers-internal, habitual, social, and environmental. We propose an ecological model of smoking cues to inform the design of mobile health (mHealth) interventions for smoking cessation. We suggest that user-triggered strategies will be most useful to address internal cues; server-triggered strategies will be most suitable in changing perceived social norms of smoking and routine smoking activities to address social and habitual cues; and context-triggered strategies will be most effective for counteracting environmental cues. The pros and cons of each approach are discussed regarding their cost-effectiveness, the potential to provide personalized assistance, and scale.

Inaccuracy of estimated resting oxygen uptake in the clinical setting.

BACKGROUND: The Fick principle (cardiac output = oxygen uptake ( O2)/systemic arterio-venous oxygen difference) is used to determine cardiac output in numerous clinical situations. However, estimated rather than measured O2 is commonly used because of complexities of the measurement, though the accuracy of estimation remains uncertain in contemporary clinical practice. METHODS AND RESULTS: From 1996 to 2005, resting O2 was measured via the Douglas bag technique in adult patients undergoing right heart catheterization. Resting O2 was estimated by each of 3 published formulae. Agreement between measured and estimated O2 was assessed overall, and across strata of body mass index, sex, and age. The study included 535 patients, with mean age 55 yrs, mean body mass index 28.4 kg/m2; 53% women; 64% non-white. Mean (±standard deviation) measured O2 was 241 ± 57 ml/min. Measured O2 differed significantly from values derived from all 3 formulae, with median (interquartile range) absolute differences of 28.4 (13.1, 50.2) ml/min, 37.7 (19.4, 63.3) ml/min, and 31.7 (14.4, 54.5) ml/min, for the formulae of Dehmer, LaFarge, and Bergstra, respectively (P<0.0001 for each). The measured and estimated values differed by >25% in 17% to 25% of patients depending on the formula used. Median absolute differences were greater in severely obese patients (body mass index > 40 kg/m2), but were not affected by sex or age. CONCLUSIONS: Estimates of resting O2 derived from conventional formulae are inaccurate, especially in severely obese individuals. When accurate hemodynamic assessment is important for clinical decision-making, O2 should be directly measured.

Homoarginine and cardiovascular outcome in the population-based Dallas Heart Study.

OBJECTIVE: The nonproteinogenic amino acid homoarginine has been postulated to have antiatherosclerotic effects as a weak substrate of nitric oxide synthase. This investigation in the population-based Dallas Heart Study (DHS) aimed to evaluate the association of homoarginine with clinical and subclinical cardiovascular outcomes. APPROACH AND RESULTS: Plasma homoarginine was measured in 3514 participants of the DHS using liquid chromatography-tandem mass spectrometry. Associations between homoarginine and major adverse cardiovascular events and all-cause mortality were analyzed using Cox proportional hazard models adjusting for cardiovascular risk factors. Linear regression was used to assess cross-sectional associations between homoarginine and subclinical cardiovascular disease, including coronary artery calcium measured by electron beam-computed tomography, and aortic plaque burden and aortic wall thickness by MRI. Median age was 43 (interquartile range, 36-52) years, with 56% women and 52% black participants. Median follow-up was 9.4 (9.0-9.8) years. Median plasma homoarginine was 2.80 (2.14-3.54) µmol/L. In multivariable models, higher homoarginine was associated with lower rate of major adverse cardiovascular events (hazard ratio, 0.86; 95% confidence interval, 0.75-0.98) and lower all-cause mortality (hazard ratio, 0.82; 0.73-0.92; per 1 log SD increase in homoarginine). Homoarginine was inversely and independently associated with aortic wall thickness (ß-estimate, -0.04; P<0.01) but not with aortic plaque burden and coronary artery calcium. CONCLUSIONS: Homoarginine is inversely associated with subclinical vascular disease and with risk for cardiovascular disease events. Additional studies are needed to evaluate whether the regulation of plasma homoarginine could emerge as a novel therapeutic option to improve outcomes in cardiovascular disease.

Predicting cardiovascular risk in type 2 diabetes: the heterogeneity challenges.

Type 2 diabetes mellitus has reached epidemic proportions around the world, and the increase in cardiovascular risk attributable to diabetes estimated to range from 2- to 4-fold poses grave public health concern. Though in some contexts type 2 diabetes has been equated with coronary heart disease equivalent risk, there is considerable evidence that incremental cardiovascular risk does not uniformly affect all people with type 2 diabetes. This heterogeneity in cardiovascular risk is multifactorial and only partially understood but is a key consideration for our understanding of the nexus of diabetes and cardiovascular disease and for the development of optimal and individualized cardiovascular risk reduction strategies. This review provides a brief synopsis of the concept of cardiovascular risk heterogeneity in diabetes, including epidemiologic evidence, discussion of established and potential determinants of heterogeneity, and clinical, research, and regulatory implications.

Type of ß-blocker use among patients with versus without diabetes after myocardial infarction.

BACKGROUND: Discharge ß-blocker prescription after myocardial infarction (MI) is recommended for all eligible patients. Numerous ß-blocker choices are presently available with variable glycometabolic effects, which could be an important consideration in patients with diabetes mellitus (DM). Whether patients with DM preferentially receive ß-blockers with favorable metabolic effects after MI and if this choice is associated with better glycemic control postdischarge is unknown. METHODS: Among patients from 24 US hospitals enrolled in an MI registry (2005-2008), we investigated the frequency of "DM-friendly" ß-blocker prescription at discharge by DM status. ß-Blockers were classified as DM-friendly (eg, carvedilol and labetalol) or non-DM-friendly (eg, metoprolol and atenolol), based on their effects on glycemic control. Hierarchical, multivariable logistic regression examined the association of DM with DM-friendly ß-blocker use. Among DM patients, we examined the association of DM-friendly ß-blockers with worsened glycemic control at 6 months after MI. RESULTS: Of 4,031 MI patients, 1,382 (34%) had DM. ß-Blockers were prescribed at discharge in 93% of patients. Diabetes mellitus-friendly ß-blocker use was low regardless of DM status, although patients with DM were more likely to be discharged on a DM-friendly ß-blocker compared with patients without DM (13.5% vs 10.3%, P = .003), an association that remained after multivariable adjustment (odds ratio 1.41, 95% CI 1.13-1.77). There was a trend toward a lower risk of worsened glucose control at 6 months in DM patients prescribed DM-friendly versus non-DM-friendly ß-blockers (Relative Risk 0.80, 95% CI 0.60-1.08). CONCLUSION: Most DM patients were prescribed non-DM-friendly ß-blockers-a practice that was associated with a trend toward worse glycemic control postdischarge. Although in need of further confirmation in larger studies, our findings highlight an opportunity to improve current practices of ß-blockers use in patients with DM.

Symmetrical dimethylarginine predicts mortality in the general population: observations from the Dallas heart study.

OBJECTIVE: Increased asymmetrical dimethylarginine (ADMA), a NO synthase inhibitor, and its congener symmetrical dimethylarginine (SDMA), predict cardiovascular and all-cause mortality in at-risk populations. Their prognostic value in the general population remains uncertain. We investigated the correlations of SDMA and ADMA with atherosclerosis and cardiovascular/all-cause mortality in the Dallas Heart Study, a multiethnic probability-based cohort aged 30 to 65 years. APPROACH AND RESULTS: SDMA and ADMA were measured by liquid chromatography-tandem mass-spectrometry (n=3523), coronary artery calcium by electron-beam computed tomography, and abdominal aortic wall thickness by MRI. In unadjusted analyses, categories of increasing SDMA and ADMA were associated with higher prevalence of cardiovascular risk factors, increased risk markers, and all-cause and cardiovascular mortality (median follow-up, 7.4 years). After adjustment for age, sex, and race, traditional cardiovascular risk factors, and renal function, SDMA and ADMA analyzed as continuous variables were associated with coronary artery calcium >10, but only SDMA was associated with abdominal aortic wall thickness. SDMA, but not ADMA, was associated with cardiovascular mortality (hazard ratio per log unit change, 3.36 [95% confidence interval, 1.49-7.59]; P=0.004). SDMA and ADMA were both associated with all-cause mortality, but after further adjustment for N-terminal pro-brain-type natriuretic peptide, high-sensitivity C-reactive protein, and high-sensitivity cardiac troponin T, only SDMA was associated with all-cause mortality (hazard ratio per log unit change, 1.86 [95% confidence interval, 1.04-3.30]; P=0.01). CONCLUSIONS: SDMA, but not ADMA, was an independent predictor of all-cause and cardiovascular mortality in a large multiethnic population-based cohort.

Discordant effects of rosiglitazone on novel inflammatory biomarkers.

BACKGROUND: Although rosiglitazone favorably affects myriad intermediate markers of atherosclerosis, it appears to increase myocardial infarction (MI) risk. We analyzed the effects of rosiglitazone on a panel of 8 novel circulating biomarkers, 4 of which are independently associated with atherosclerosis: lymphotoxin ß receptor, peptidoglycan recognition protein 1, chemokine ligand 23, and soluble receptor for advanced glycation end products (sRAGE) as well as on high-sensitivity C-reactive protein (hs-CRP). METHODS: Blood samples were analyzed at baseline and after 6 months of study treatment from subjects with type 2 diabetes with or at high risk for coronary artery disease in a randomized trial comparing rosiglitazone versus placebo. RESULTS: Data from 111 subjects (rosiglitazone 55, placebo 56) were analyzed. Mean age was 56 years, 41% were women, and 66% were nonwhite. Compared with baseline values, rosiglitazone adversely affected levels of lymphotoxin ß receptor (1.7 vs 2.4 ng/mL, P = .002), peptidoglycan recognition protein 1 (29.0 vs 30.1 ng/mL, P = .01), and chemokine ligand 23 (0.76 vs 0.84 ng/mL, P = .02) and favorably affected levels of sRAGE (inversely associated with atherosclerosis, 1.1 vs 1.4 ng/mL, P = .003) and hs-CRP (0.42 vs 0.31 ng/mL, P = .02); no changes were observed with rosiglitazone in the other biomarkers. In the placebo group, change was observed only for sRAGE (1.0 vs 1.1 ng/mL, P = .046). CONCLUSION: Rosiglitazone adversely affected 3 novel biomarkers and favorably affected a fourth previously associated with atherosclerosis while improving hs-CRP, as has previously been shown. Whether these complex effects on circulating inflammatory biomarkers contribute to the signal of increased MI risk with rosiglitazone and whether pioglitazone has similar effects warrant further investigation.

Cardiovascular Risk Factor Knowledge among Monolingual Hispanics.

Hispanics in the United States have worse cardiovascular disease (CVD) risk factor profiles than non-Hispanic Whites. Cardiovascular health literacy is important for health promotion but is not well characterized among monolingual Spanish-speaking Hispanics outside of health care settings. We recruited Hispanic participants (N=235) from a community-based health fair in Denver, Colorado. A total of 182 participants (77%) completed a subsequent language-congruent telephone survey to assess CVD risk-factor knowledge. Of these, 174 self-identified as monolingual Spanish-speaking, and constituted the analysis cohort. Cardiovascular disease risk knowledge score was defined as the number of established risk factors an individual participant could name (out of 10 pre-specified), and multivariable regression analyses were conducted to determine factors independently associated with knowledge. The mean knowledge score for the cohort was 2.2 ± 1.1 out of 10. This suggests an unmet need for tailored educational interventions beyond simple screening events.

A Point-of-Care Algorithm to Guide Proper Device Selection for Ambulatory Electrocardiography.

In the outpatient setting, ambulatory electrocardiography is the most frequently used diagnostic modality for the evaluation of patients in whom cardiac arrhythmias or conduction abnormalities are suspected. Proper selection of the device type and monitoring duration is critical for optimizing diagnostic yield and cost-effective resource utilization. However, despite guidance from major professional societies, the lack of systematic guidance for proper test selection in many institutions results in the need for repeat testing, which leads to not only increased resource utilization and cost of care, but also suboptimal patient care. To address this unmet need at our own institution, we formed a multidisciplinary panel to develop a concise, yet comprehensive algorithm, incorporating the most common indications for ambulatory electrocardiography, to efficiently guide clinicians to the most appropriate test option for a given clinical scenario, with the goal of maximizing diagnostic yield and optimizing resource utilization. The algorithm was designed as a single-page, color-coded flowchart to be utilized both as a rapid reference guide in printed form, and a decision support tool embedded within the electronic medical records system at the point of order entry. We believe that systematic adoption of this algorithm will optimize diagnostic efficiency, resource utilization, and importantly, patient care and satisfaction.

Elements of Social Convoy Theory in Mobile Health for Palliative Care: Scoping Review.

BACKGROUND: Mobile health (mHealth) provides a unique modality for improving access to and awareness of palliative care among patients, families, and caregivers from diverse backgrounds. Some mHealth palliative care apps exist, both commercially available and established by academic researchers. However, the elements of family support and family caregiving tools offered by these early apps is unknown. OBJECTIVE: The objective of this scoping review was to use social convoy theory to describe the inclusion and functionality of family, social relationships, and caregivers in palliative care mobile apps. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Review guidelines, a systematic search of palliative care mHealth included (1) research-based mobile apps identified from academic searches published between January 1, 2010, and March 31, 2019 and (2) commercially available apps for app stores in April 2019. Two reviewers independently assessed abstracts, app titles, and descriptions against the inclusion and exclusion criteria. Abstracted data covered app name, research team or developer, palliative care element, target audience, and features for family support and caregiving functionality as defined by social convoy theory. RESULTS: Overall, 10 articles describing 9 individual research-based apps and 22 commercially available apps were identified. Commercially available apps were most commonly designed for both patients and social convoys, whereas the majority of research apps were designed for patient use only. CONCLUSIONS: Results suggest there is an emerging presence of apps for patients and social convoys receiving palliative care; however, there are many needs for developers and researchers to address in the future. Although palliative care mHealth is a growing field, additional research is needed for apps that embrace a team approach to information sharing, target family- and caregiver-specific issues, promote access to palliative care, and are comprehensive of palliative needs.

Cardiovascular disease and type 2 diabetes mellitus: regulating glucose and regulating drugs.

Type 2 diabetes mellitus is a major and increasingly prevalent independent risk factor for cardiovascular morbidity and mortality worldwide. Glycemic control is a target of therapy and a principal marker of therapeutic success in diabetes, but whether lowering glucose is accompanied by a commensurate reduction in cardiovascular risk is a matter of ongoing controversy. It has become increasingly apparent from recent large-scale clinical outcome trials that glucose lowering is a poor predictor of cardiovascular outcome, and several instances of unexpectedly increased cardiovascular risk with antihyperglycemic drugs have sounded the alarm with regulatory agencies. This article reviews the critical facts that have led to a recent shift in the regulation of glucose-lowering drugs and makes the case for why new and existing antidiabetic medications should be assessed in clinical trials of cardiovascular outcome.

Advancing evidence-based digital health through an innovative research environment: an academic-industry collaboration case report.

The proliferation of technology enthuses clinicians, researchers, and entrepreneurs to revolutionize health care and care delivery. Intersecting in the field of digital health, academic-industry collaboration (AIC) play a critical role in advancing evidence-based innovations into real world application. AIC models vary, but historically have not included the strong emphasis on rapid research and discovery that the digital health field demands. Due to the voluminous availability of real time patient and client data, academic health centers offer a rich interdisciplinary environment to develop, pilot and evaluate innovations in pragmatic settings. Despite the opportunity between academic health centers and industry to advance digital health innovation through rapid research, limited evidence exists of such collaboration. The purpose of this case report is to examine an AIC facilitating research of new health technologies within an academic health center. This paper presents a case report involving collaboration between diverse technology industry partners and an academic health center that encompasses a university health system (UCHealth), a university technology transfer office (CU Innovations), an innovation center (CARE Innovation Center), and research collaborators (mHealth Impact Laboratory). Case assertions discuss the lessons learned and recommendations when implementing such collaboration in practice. The principal finding is that academic health centers offer an innovative environment for AIC in digital health. Collaborations between academia and industry provide much promise in ensuring health innovations are scientifically sound while meeting the needs of a rapidly evolving technical climate.

Racial Differences in Cardiovascular Biomarkers in the General Population.

Background The incidence and clinical manifestations of cardiovascular disease (CVD) differ between blacks and whites. Biomarkers that reflect important pathophysiological pathways may provide a window to allow deeper understanding of racial differences in CVD. Methods and Results The study included 2635 white and black participants from the Dallas Heart Study who were free from existing CVD. Cross-sectional associations between race and 32 biomarkers were evaluated using multivariable linear regression adjusting for age, traditional CVD risk factors, imaging measures of body composition, renal function, insulin resistance, left ventricular mass, and socioeconomic factors. In fully adjusted models, black women had higher lipoprotein(a), leptin, d-dimer, osteoprotegerin, antinuclear antibody, homoarginine, suppression of tumorigenicity-2, and urinary microalbumin, and lower adiponectin, soluble receptor for advanced glycation end products and N-terminal pro-B-type natriuretic peptide versus white women. Black men had higher lipoprotein(a), leptin, d-dimer, high-sensitivity C-reactive protein, antinuclear antibody, symmetrical dimethylarginine, homoarginine, high-sensitivity cardiac troponin T, suppression of tumorigenicity-2, and lower adiponectin, soluble receptor for advanced glycation end products, and N-terminal pro-B-type natriuretic peptide versus white men. Adjustment for biomarkers that were associated with higher CVD risk, and that differed between blacks and whites, attenuated the risk for CVD events in black women (unadjusted hazard ratio 2.05, 95% CI 1.32, 3.17 and adjusted hazard ratio 1.15, 95% CI 0.69, 1.92) and black men (unadjusted hazard ratio 2.39, 95% CI 1.64, 3.46, and adjusted hazard ratio 1.21, 95% CI 0.76, 1.95). Conclusions Significant racial differences were seen in biomarkers reflecting lipids, adipokines, and biomarkers of endothelial function, inflammation, myocyte injury, and neurohormonal stress, which may contribute to racial differences in the development and complications of CVD.

Identifying Familial Hypercholesterolemia Using a Blood Donor Screening Program With More Than 1 Million Volunteer Donors.

Importance: Familial hypercholesterolemia is an autosomal-dominant disorder that often causes premature coronary artery disease. Unfortunately, familial hypercholesterolemia remains largely undiagnosed. Objective: To estimate the prevalence of familial hypercholesterolemia in a population of blood donors. Design: This analysis of deidentified data from blood donors 16 years and older who donated to Carter BloodCare, one of the largest independent blood programs in the United States, between January 2002 and December 2016. Carter BloodCare, which serves a population of about 8 million in Texas, routinely measures total nonfasting serum cholesterol levels as part of a donor health screening program. Data analysis occurred from October 2017 to March 2019. Exposure: Blood donation. Main Outcomes and Measures: Familial hypercholesterolemia was defined using the Make Early Diagnosis to Prevent Early Death general population criteria, with total nonfasting serum cholesterol thresholds of 270, 290, 340, and 360 mg/dL for donors younger than 20 years, 20 to 29 years, 30 to 39 years, and 40 years or older, respectively (to convert cholesterol values to mmol/L, multiply by 0.0259). For repeated donors, the maximum observed total cholesterol level was used for analyses. Results: The study included 1 178 102 individual donors with a total of 3 038 420 blood donations. Of all individual donors (median total cholesterol level, 183 [interquartile range (IQR), 157-212] mg/dL; median age, 32 [IQR, 19-47] years; 619 583 [52.6%] women), a total of 3473 individuals (or 1 in every 339) met criteria for familial hypercholesterolemia. This group had a median (IQR) total cholesterol of 332 (297-377) mg/dL. Estimated prevalence was higher at younger ages (<30 years: 1:257) compared with older ages (≥30 years: 1:469; P < .001) and in men (1:327) compared with women (1:351; P = .03). Among 2219 repeated donors who met familial hypercholesterolemia criteria at least once, 3116 of 10 833 total donations (28.8%) met FH criteria. Conclusions and Relevance: The prevalence of familial hypercholesterolemia using the Make Early Diagnosis to Prevent Early Death criteria in a large cohort of blood donors was similar to the estimated prevalence of this disorder in the general population. The blood donor screening program could be a novel strategy to detect and notify individuals with potential familial hypercholesterolemia, particularly younger individuals in whom early detection and treatment is especially helpful, as well as guide cascade screening.

A Test in Context: Hemoglobin A1c and Cardiovascular Disease.

Measurement of glycated hemoglobin (HbA1c), the most widely accepted indicator of long-term glycemic exposure, is central for the diagnosis and management of diabetes mellitus. Levels of HbA1c track epidemiologically with diabetic complications, and glycemic control, as reflected by HbA1c reduction, results in decreased risk of microvascular complications, including diabetic kidney disease, neuropathy, and retinopathy. The relationship between HbA1c reduction and cardiovascular disease prevention in patients with diabetes is more complex, with data from large randomized trials published over the past decade providing clear evidence that lowering of HbA1c per se is an inadequate marker for a therapeutic regimen's impact on cardiovascular outcomes and patient survival. Recent revisions in professional society guidelines moved away from uniform recommendations and toward a more nuanced, patient-centered approach to HbA1c therapeutic targets. The context and key evidence underpinning these recent changes are discussed in this paper, alongside a brief overview of HbA1c contemporary assays and their limitations.

Effect of treatment with rosiglitazone on high-sensitivity cardiac troponin levels among patients with type 2 diabetes mellitus.

OBJECTIVE: To assess the impact of intermediate-term treatment with rosiglitazone on high-sensitivity cardiac troponin T levels among patients with type 2 diabetes mellitus with or at high risk of coronary artery disease. METHODS: High-sensitivity cardiac troponin T level was measured at baseline and after 6 months of study treatment in a randomized trial comparing rosiglitazone versus placebo in patients with type 2 diabetes and prevalent cardiovascular disease or multiple cardiovascular disease risk factors. Univariable and multivariable linear regression analyses were performed to assess the effect of rosiglitazone versus placebo on high-sensitivity cardiac troponin T levels. RESULTS: The study included 150 randomized participants, of whom 106 had paired baseline and end-of-study blood samples for analysis (mean age: 56 ± 8 years, 42% women; 8.8 years average type 2 diabetes duration; mean haemoglobin A1c of 7.5). Almost all study participants (93%) had detectable high-sensitivity cardiac troponin T (⩾ 3 ng/L) at baseline, including 23% with high-sensitivity cardiac troponin T levels exceeding the threshold commonly used to diagnose myocardial infarction (⩾ 14 ng/L). Change in high-sensitivity cardiac troponin T levels from baseline to follow-up was not significantly different between rosiglitazone and placebo groups (p = 0.316). CONCLUSION: Rosiglitazone did not impact high-sensitivity cardiac troponin T levels, adding to the growing body of literature suggesting that the incremental heart failure risk associated with rosiglitazone is not mediated by direct myocardial injury.

High prevalence of elevated haemoglobin A1C among adolescent blood donors: Results from a voluntary screening programme including 31,546 adolescents.

More than 1 in 10 US adolescents have prediabetes or diabetes, and elevated glycosylated haemoglobin (HbA1C) in youth is associated with increased risk of death before the age of 55 years. We conducted a prospective, cross-sectional study of 31,546 consecutive volunteer blood donors, 16-19 years of age, who donated blood during school blood drives between 1 September 2011 and 21 December 2012 in Texas. In the overall cohort, the prevalence of elevated HbA1C was 11.5%, including 11.0% in the prediabetes range (HbA1C 5.7%-6.4%) and 0.5% in the diabetes range (HbA1C ⩾ 6.5%). The prevalence of elevated HbA1C was higher in boys compared with girls (15.7% vs. 7.9%, p < 0.001) and was especially high in racial/ethnic minorities (Blacks 32.7%, Asians 19.7%, Hispanics 13.1%) compared with Whites (8.0%, p < 0.001). There was a significant increase in total cholesterol and blood pressure across categories of increasing HbA1C in the overall cohort and stratified by sex and race/ethnicity. Blood donation programmes can serve as unique portals for health screening with potential for intervention in adolescents.