An Unusual Case of Asystole following Penetrating Neck Trauma and Anoxic Brain Injury

Bradycardia and transient asystole are well-described sequelae of a myriad of neurologic insults, ranging from focal to generalized injuries. Increased vagal tone also predisposes many individuals, particularly adolescents, to transient neurally mediated bradyarrhythmia. However, prolonged periods of sinus arrest without junctional or ventricular escape are quite rare, even after significant neurologic injury. We describe the case of a 17-year-old man who presented with anoxic brain injury secondary to hemorrhagic shock from a stab wound to the neck. His recovery was complicated by prolonged periods of sinus arrest and asystole, lasting over 60 seconds per episode. This case illustrates that sustained asystolic episodes may occur following significant neurologic injury, and may continue to recur even months after an initial insult. Pacemaker implantation for such patients should be strongly considered

Association of Exhaled Carbon Monoxide With Stroke Incidence and Subclinical Vascular Brain Injury

Background and purposeExhaled carbon monoxide (CO) is associated with cardiometabolic traits, subclinical atherosclerosis, and cardiovascular disease, but its specific relations with stroke are unexplored. We related exhaled CO to magnetic resonance imaging measures of subclinical cerebrovascular disease cross-sectionally and to incident stroke/transient ischemic attack prospectively in the Framingham Offspring study.MethodsWe measured exhaled CO in 3313 participants (age 59±10 years; 53% women), and brain magnetic resonance imaging was available in 1982 individuals (age 58±10 years; 54% women). Participants were analyzed according to tertiles of exhaled CO concentration.ResultsIn age- and sex-adjusted models, the highest tertile of exhaled CO was associated with lower total cerebral brain volumes, higher white-matter hyperintensity volumes, and greater prevalence of silent cerebral infarcts (P<0.05 for all). The results for total cerebral brain volume and white-matter hyperintensity volume were consistent after removing smokers from the sample, and the association with white-matter hyperintensity volume persisted after multivariable adjustment (P=0.04). In prospective analyses (mean follow-up 12.9 years), higher exhaled CO was associated with 67% (second tertile) and 97% (top tertile) increased incidence of stroke/transient ischemic attack relative to the first tertile that served as referent (P<0.01 for both). These results were consistent in nonsmokers and were partially attenuated upon adjustment for vascular risk factors.ConclusionsIn this large, community-based sample of individuals without clinical stroke/transient ischemic attack at baseline, higher exhaled CO was associated with a greater burden of subclinical cerebrovascular disease cross-sectionally and with increased risk of stroke/transient ischemic attack prospectively. Further investigation is necessary to explore the biological mechanisms linking elevated CO with stroke

The inflammatory proteome, obesity, and medical weight loss and regain in humans

ObjectiveWeight regain occurs after medical weight loss via mechanisms of post-weight-loss “metabolic adaptation.” The relationship of inflammatory proteins with weight loss/regain was studied to determine a role for inflammation in metabolic adaptation.MethodsSeventy-four proteins central to inflammation and immune regulation (Olink) were analyzed in plasma from up to 490 participants in a trial of medical weight-loss maintenance. Cross-sectional and longitudinal associations of proteins with weight were measured using linear and mixed effects regression models and t testing, with replication in the Framingham Heart Study.ResultsBroad changes in the inflammatory proteome were observed among the study cohort (60% women, 35% African American) with initial weight loss of ≈8 kg from a median 94 kg at study entry (33/74 proteins; 7 increased; 26 decreased), many of which tracked with weight regain of median ≈2 kg over the next 30 months. Ten proteins were associated with different rates of weight regain, some specifying pathways of chemotaxis and innate immune responses. Several of the observed protein associations were also linked to prevalent obesity in the Framingham Heart Study.ConclusionsBroad changes in the inflammatory proteome track with changes in weight and may identify specific pathways that modify patterns of weight regain.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/175408/1/oby23587.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175408/2/oby23587-sup-0001-FigureS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/175408/3/oby23587_am.pd

Circulating metabolites may illustrate relationship of alcohol consumption with cardiovascular disease

BackgroundMetabolite signatures of long-term alcohol consumption are lacking. To better understand the molecular basis linking alcohol drinking and cardiovascular disease (CVD), we investigated circulating metabolites associated with long-term alcohol consumption and examined whether these metabolites were associated with incident CVD.MethodsCumulative average alcohol consumption (g/day) was derived from the total consumption of beer, wine, and liquor on average of 19 years in 2428 Framingham Heart Study Offspring participants (mean age 56 years, 52% women). We used linear mixed models to investigate the associations of alcohol consumption with 211 log-transformed plasma metabolites, adjusting for age, sex, batch, smoking, diet, physical activity, BMI, and familial relationship. Cox models were used to test the association of alcohol-related metabolite scores with fatal and nonfatal incident CVD (myocardial infarction, coronary heart disease, stroke, and heart failure).ResultsWe identified 60 metabolites associated with cumulative average alcohol consumption (p < 0.05/211 ≈ 0.00024). For example, 1 g/day increase of alcohol consumption was associated with higher levels of cholesteryl esters (e.g., CE 16:1, beta = 0.023 ± 0.002, p = 6.3e - 45) and phosphatidylcholine (e.g., PC 32:1, beta = 0.021 ± 0.002, p = 3.1e - 38). Survival analysis identified that 10 alcohol-associated metabolites were also associated with a differential CVD risk after adjusting for age, sex, and batch. Further, we built two alcohol consumption weighted metabolite scores using these 10 metabolites and showed that, with adjustment age, sex, batch, and common CVD risk factors, the two scores had comparable but opposite associations with incident CVD, hazard ratio 1.11 (95% CI = [1.02, 1.21], p = 0.02) vs 0.88 (95% CI = [0.78, 0.98], p = 0.02).ConclusionsWe identified 60 long-term alcohol consumption-associated metabolites. The association analysis with incident CVD suggests a complex metabolic basis between alcohol consumption and CVD

Circulating metabolite profile in young adulthood identifies long-term diabetes susceptibility: the Coronary Artery Risk Development in Young Adults (CARDIA) study

Aims/hypothesis: The aim of this work was to define metabolic correlates and pathways of diabetes pathogenesis in young adults during a subclinical latent phase of diabetes development. Methods: We studied 2083 young adults of Black and White ethnicity in the prospective observational cohort Coronary Artery Risk Development in Young Adults (CARDIA) study (mean ± SD age 32.1 ± 3.6 years; 43.9% women; 42.7% Black; mean ± SD BMI 25.6 ± 4.9 kg/m2) and 1797 Framingham Heart Study (FHS) participants (mean ± SD age 54.7 ± 9.7 years; 52.1% women; mean ± SD BMI 27.4 ± 4.8 kg/m2), examining the association of comprehensive metabolite profiles with endophenotypes of diabetes susceptibility (adipose and muscle tissue phenotypes and systemic inflammation). Statistical learning techniques and Cox regression were used to identify metabolite signatures of incident diabetes over a median of nearly two decades of follow-up across both cohorts. Results: We identified known and novel metabolites associated with endophenotypes that delineate the complex pathophysiological architecture of diabetes, spanning mechanisms of muscle insulin resistance, inflammatory lipid signalling and beta cell metabolism (e.g. bioactive lipids, amino acids and microbe- and diet-derived metabolites). Integrating endophenotypes of diabetes susceptibility with the metabolome generated two multi-parametric metabolite scores, one of which (a proinflammatory adiposity score) was associated with incident diabetes across the life course in participants from both the CARDIA study (young adults; HR in a fully adjusted model 2.10 [95% CI 1.72, 2.55], p<0.0001) and FHS (middle-aged and older adults; HR 1.33 [95% CI 1.14, 1.56], p=0.0004). A metabolite score based on the outcome of diabetes was strongly related to diabetes in CARDIA study participants (fully adjusted HR 3.41 [95% CI 2.85, 4.07], p<0.0001) but not in the older FHS population (HR 1.15 [95% CI 0.99, 1.33], p=0.07). Conclusions/interpretation: Selected metabolic abnormalities in young adulthood identify individuals with heightened diabetes risk independent of race, sex and traditional diabetes risk factors. These signatures replicate across the life course

Dietary metabolic signatures and cardiometabolic risk

Aims: Observational studies of diet in cardiometabolic-cardiovascular disease (CM-CVD) focus on self-reported consumption of food or dietary pattern, with limited information on individual metabolic responses to dietary intake linked to CM-CVD. Here, machine learning approaches were used to identify individual metabolic patterns related to diet and relation to long-term CM-CVD in early adulthood. Methods and results: In 2259 White and Black adults (age 32.1 ± 3.6 years, 45% women, 44% Black) in the Coronary Artery Risk Development in Young Adults (CARDIA) study, multivariate models were employed to identify metabolite signatures of food group and composite dietary intake across 17 food groups, 2 nutrient groups, and healthy eating index-2015 (HEI2015) diet quality score. A broad array of metabolites associated with diet were uncovered, reflecting food-related components/catabolites (e.g. fish and long-chain unsaturated triacylglycerols), interactions with host features (microbiome), or pathways broadly implicated in CM-CVD (e.g. ceramide/sphingomyelin lipid metabolism). To integrate diet with metabolism, penalized machine learning models were used to define a metabolite signature linked to a putative CM-CVD-adverse diet (e.g. high in red/processed meat, refined grains), which was subsequently associated with long-term diabetes and CVD risk numerically more strongly than HEI2015 in CARDIA [e.g. diabetes: standardized hazard ratio (HR): 1.62, 95% confidence interval (CI): 1.32-1.97, P < 0.0001; CVD: HR: 1.55, 95% CI: 1.12-2.14, P = 0.008], with associations replicated for diabetes (P < 0.0001) in the Framingham Heart Study. Conclusion: Metabolic signatures of diet are associated with long-term CM-CVD independent of lifestyle and traditional risk factors. Metabolomics improves precision to identify adverse consequences and pathways of diet-related CM-CVD