Explore the vast range of titles available.

Background Plasma ceramides and sphingomyelins have been independently linked to diabetes risk, glucose and insulin levels, and the risk of several cardiovascular (CVD) outcomes. However, whether individual ceramide and sphingomyelin species contribute to CVD risk among people with type 2 diabetes is uncertain. Our goal was to evaluate associations of 4 ceramide and 4 sphingomyelin species with incident CVD in a longitudinal population-based study among American Indians with diabetes. Methods This analysis included participants with prevalent type 2 diabetes from two cohorts: a prospective cohort of 597 participants in the Strong Heart Family Study (116 incident CVD cases; mean age: 49 years; average length of follow-up: 14 years), and a nested case–control sample of 267 participants in the Strong Heart Study (78 cases of CVD and 189 controls; mean age: 61 years; average time until incident CVD in cases: 3.8 years). The average onset of diabetes was 7 years prior to sphingolipid measurement. Sphingolipid species were measured using liquid chromatography and mass spectrometry. Cox regression and logistic regression were used to assess associations of sphingolipid species with incident CVD; results were combined across cohorts using inverse-variance weighted meta-analysis. Results There were 194 cases of incident CVD in the two cohorts. In meta-analysis of the 2 cohort results, higher plasma levels of Cer-16 (ceramide with acylated palmitic acid) were associated with higher CVD risk (HR per two-fold higher Cer-16: 1.85; 95% CI 1.05–3.25), and higher plasma levels of sphingomyelin species with a very long chain saturated fatty acid were associated with lower CVD risk (HR per two-fold higher SM-22: 0.48; 95% CI 0.26–0.87), although none of the associations met our pre-specified threshold for statistical significance of p = 0.006. Conclusions While replication of the findings from the SHS in other populations is warranted, our findings add to a growing body of research suggesting that ceramides, in particular Cer-16, not only are associated with higher diabetes risk, but may also be associated with higher CVD risk after diabetes onset. We also find support for the hypothesis that sphingomyelins with a very long chain saturated fatty acid are associated with lower CVD risk among adults with type 2 diabetes.

Sick sinus syndrome (SSS) is a common indication for pacemaker implantation. Limited information exists on the association of sick sinus syndrome (SSS) with mortality and cardiovascular disease (CVD) in the general population. We studied 19,893 men and women age 45 and older in the Atherosclerosis Risk in Communities (ARIC) study and the Cardiovascular Health Study (CHS), two community-based cohorts, who were without a pacemaker or atrial fibrillation (AF) at baseline. Incident SSS cases were validated by review of medical charts. Incident CVD and mortality were ascertained using standardized protocols. Multivariable Cox models were used to estimate the association of incident SSS with selected outcomes. During a mean follow-up of 17 years, 213 incident SSS events were identified and validated (incidence, 0.6 events per 1,000 person-years). After adjustment for confounders, SSS incidence was associated with increased mortality (hazard ratio [HR] 1.39, 95% confidence interval [CI] 1.14-1.70), coronary heart disease (HR 1.72, 95%CI 1.11-2.66), heart failure (HR 2.87, 95%CI 2.17-3.80), stroke (HR 1.56, 95%CI 0.99-2.46), AF (HR 5.75, 95%CI 4.43-7.46), and pacemaker implantation (HR 53.7, 95%CI 42.9-67.2). After additional adjustment for other incident CVD during follow-up, SSS was no longer associated with increased mortality, coronary heart disease, or stroke, but remained associated with higher risk of heart failure (HR 2.00, 95%CI 1.51-2.66), AF (HR 4.25, 95%CI 3.28-5.51), and pacemaker implantation (HR 25.2, 95%CI 19.8-32.1). Individuals who develop SSS are at increased risk of death and CVD. The mechanisms underlying these associations warrant further investigation.

CYP2J2, a member of the Cytochrome P450 family of enzymes, is the most abundant epoxygenase in the heart and has multifunctional properties including bioactivation of arachidonic acid to epoxyeicosatrienoic acids, which, in turn, have been implicated in mediating several cardiovascular conditions. Using a proteomic approach, we found that CYP2J2 expression is lower in cardiac tissue from patients with cardiomyopathy compared to controls. In order to better elucidate the complex role played by CYP2J2 in cardiac cells, we performed targeted silencing of CYP2J2 expression in human adult ventricular cardiomyocytes and interrogated whole genome transcriptional responses. We found that knockdown of CYP2J2 elicits widespread alterations in gene expression of ventricular cardiomyocytes and leads to the activation of a diverse repertoire of programs, including those involved in ion channel signaling, development, extracellular matrix, and metabolism. Several members of the differentially up-regulated ion channel module have well-known pathogenetic roles in cardiac dysrhythmias. By leveraging causal network and upstream regulator analysis, we identified several candidate drivers of the observed transcriptional response to CYP2J2 silencing; these master regulators have been implicated in aberrant cardiac remodeling, heart failure, and myocyte injury and repair. Collectively, our study demonstrates that CYP2J2 plays a central and multifaceted role in cardiomyocyte homeostasis and provides a framework for identifying critical regulators and pathways influenced by this gene in cardiovascular health and disease.

Newly diagnosed atrial fibrillation (AF) during severe sepsis is associated with increased risks of in-hospital stroke and mortality. However, the prevalence, incidence, and risk factors associated with AF during the sepsis syndromes are unclear. We identified patients with preexisting, newly diagnosed, or no AF in a nationally representative 5% sample of Medicare beneficiaries hospitalized with sepsis between 2004 and 2007. We identified multivariable-adjusted demographic and clinical characteristics associated with development of newly diagnosed AF during a sepsis hospitalization. A total of 60,209 beneficiaries had a sepsis hospitalization. Mean age was 80.2 years, 44.4% were men, and 83.1% were white. Atrial fibrillation occurred during 25.5% (95% CI 25.2-25.9) of sepsis hospitalizations, including 18.3% (18.0%-18.7%) with preexisting AF and 7.2% (7.0%-7.4%) with newly diagnosed AF. Patients with sepsis requiring intensive care had a greater risk of newly diagnosed AF (10.7%, 95% CI 10.3%-11.1%) compared with patients who did not require intensive care (4.4%, 4.2%-4.5%, P < .001). In multivariable analysis, factors associated with newly diagnosed AF during sepsis included older age, white race, acute organ dysfunction, intensive care unit admission, mechanical ventilation, right heart catheterization, diagnosis of endocarditis, and coronary artery bypass graft surgery. Cardiovascular comorbid conditions generally were not associated with increased risk for newly diagnosed AF during sepsis. Atrial fibrillation is common among critically ill patients with sepsis. Acute factors, rather than preexisting cardiovascular comorbid conditions, are associated with increased risk for newly diagnosed AF during sepsis, suggesting that mechanisms of newly diagnosed AF during sepsis may differ from the general population of patients with AF.

Atrial fibrillation (AF) is associated with an increased risk of ischemic stroke and cardiovascular (CV) death. Whether modifiable lifestyle risk factors are associated with these CV outcomes in AF is unknown. Among Atherosclerosis Risk in Communities (ARIC) study and Cardiovascular Health Study (CHS) participants with incident AF, we estimated the risk of composite endpoint of ischemic stroke or CV death associated with candidate modifiable risk factor (smoking, heavy alcohol consumption, or high body mass index [BMI]), and computed the C-statistic, net reclassification improvement (NRI), and integrated discrimination improvement (IDI) of incorporating each factor into the CHA2DS2-VASc. Among 1222 ARIC (mean age: 63.4) and 756 CHS (mean age: 79.1) participants with incident AF, during mean follow-up of 6.9 years and 5.7 years, there were 332 and 335 composite events respectively. Compared with never smokers, current smokers had a higher incidence of the composite endpoint in ARIC [HR: 1.65 (1.21-2.26)] but not in CHS [HR: 1.05 (0.69-1.61)]. In ARIC, the addition of current smoking did not improve risk prediction over and above the CHA2DS2-VASc. No significant associations were observed with alcohol consumption or BMI with CVD outcomes in AF patients from either cohort. Smoking is associated with an increased risk of ischemic stroke or CV death in ARIC, which comprised mostly middle-aged to young-old (65-74 years), but not in CHS, which comprised mostly middle-old or oldest-old (≥75 years) adults with AF. However, addition of smoking to the CHA2DS2-VASc score did not improve risk prediction of these outcomes.

To evaluate the association of salt consumption with blood pressure in Viet Nam, a developing country with a high level of salt consumption. Analysis of a nationally representative sample of Vietnamese adults 25-65 years of age who were surveyed using the World Health Organization STEPwise approach to Surveillance protocol. Participants who reported acute illness, pregnancy, or current use of antihypertensive medications were excluded. Daily salt consumption was estimated from fasting mid-morning spot urine samples. Associations of salt consumption with systolic blood pressure and prevalent hypertension were assessed using adjusted linear and generalized linear models. Interaction terms were tested to assess differences by age, smoking, alcohol consumption, and rural/urban status. The analysis included 2,333 participants (mean age: 37 years, 46% male, 33% urban). The average estimated salt consumption was 10g/day. No associations of salt consumption with blood pressure or prevalent hypertension were observed at a national scale in men or women. The associations did not differ in subgroups defined by age, smoking, or alcohol consumption; however, associations differed between urban and rural participants (p-value for interaction of urban/rural status with salt consumption, p = 0.02), suggesting that higher salt consumption may be associated with higher systolic blood pressure in urban residents but lower systolic blood pressure in rural residents. Although there was no evidence of an association at a national level, associations of salt consumption with blood pressure differed between urban and rural residents in Viet Nam. The reasons for this differential association are not clear, and given the large rate of rural to urban migration experienced in Viet Nam, this topic warrants further investigation.

Abstract Background Recent studies suggest that associations of ceramides (Cer) and sphingomyelins (SM) with health outcomes differ according to the fatty acid acylated to the sphingoid backbone. The purpose of this study was to assess associations of Cer and SM species with mortality. Methods The study population included participants from the Cardiovascular Health Study (CHS), a community-based cohort of adults aged ≥65 years who were followed from 1992–2015 (n = 4612). Associations of plasma Cer and SM species carrying long-chain (i.e., 16:0) and very-long-chain (i.e., 20:0, 22:0, 24:0) saturated fatty acids with mortality were assessed using Cox proportional hazards models. Results During a median follow-up of 10.2 years, 4099 deaths occurred. High concentrations of Cer and SM carrying fatty acid 16:0 were each associated with an increased risk of mortality. Conversely, high concentrations of several ceramide and sphingomyelin species carrying longer fatty acids were each associated with a decreased risk of mortality. The hazard ratios for total mortality per 2-fold difference in each Cer and SM species were: 1.89 (95% CI), 1.65–2.17 for Cer-16, 0.79 (95% CI, 0.70–0.88) for Cer-22, 0.74 (95% CI, 0.65–0.84) for Cer-24, 2.51 (95% CI, 2.01–3.14) for SM-16, 0.68 (95% CI, 0.58–0.79) for SM-20, 0.57 (95% CI, 0.49–0.67) for SM-22, and 0.66 (0.57–0.75) for SM-24. We found no association of Cer-20 with risk of death. Conclusions Associations of Cer and SM with the risk of death differ according to the length of their acylated saturated fatty acid. Future studies are needed to explore mechanisms underlying these relationships.

Background More than six million American Indians live in the United States, and an estimated 1.6 million will be aged ≥65 years old by 2050 tripling in numbers since 2012. Physical functioning and related factors in this population are poorly understood. Our study aimed to assess lower body functioning and identify the prevalence and correlates of “good” functioning in a multi-tribe, community-based sample of older American Indians. Methods Assessments used the Short Physical Performance Battery (SPPB). “Good” lower body functioning was defined as a total SPPB score of ≥10. Potential correlates included demographic characteristics, study site, anthropometrics, cognitive functioning, depressive symptomatology, grip strength, hypertension, diabetes mellitus, heart disease, prior stroke, smoking, alcohol use, and over-the-counter medication use for arthritis or pain. Data were collected between 2010 and 2013 by the Cerebrovascular Disease and Its Consequences in American Indians Study from community-dwelling adults aged ≥60 years ( n  = 818). Results The sample’s mean age was 73 ± 5.9 years. After adjustment for age and study site, average SPPB scores were 7.0 (95% CI, 6.8, 7.3) in women and 7.8 (95% CI, 7.5, 8.2) in men. Only 25% of the sample were classified with “good” lower body functioning. When treating lower body functioning as a continuous measure and adjusting for age, gender, and study site, the correlates of better functioning that we identified were younger age, male gender, married status, higher levels of education, higher annual household income, Southern Plains study site, lower waist-hip ratio, better cognitive functioning, stronger grip strength, lower levels of depressive symptomatology, alcohol consumption, and the absence of hypertension, diabetes mellitus, and heart disease. In our fully adjusted models, correlates of “good” lower body functioning were younger age, higher annual household income, better cognitive functioning, stronger grip, and the absence of diabetes mellitus and heart disease. Conclusions These results suggest that “good” lower body functioning is uncommon in this population, whereas its correlates are similar to those found in studies of other older adult populations. Future efforts should include the development or cultural tailoring of interventions to improve lower body functioning in older American Indians.

COVID‐19 has significant case fatality. Glucocorticoids are the only treatment shown to improve survival, but only among patients requiring supplemental oxygen. WHO advises patients to seek medical care for “trouble breathing,” but hypoxemic patients frequently have no respiratory symptoms. Our cohort study of hospitalized COVID‐19 patients shows that respiratory symptoms are uncommon and not associated with mortality. By contrast, objective signs of respiratory compromise—oxygen saturation and respiratory rate—are associated with markedly elevated mortality. Our findings support expanding guidelines to include at‐home assessment of oxygen saturation and respiratory rate in order to expedite life‐saving treatments patients to high‐risk COVID‐19 patients.