Serum n-6 polyunsaturated fatty acids and risk of atrial fibrillation: the Kuopio Ischaemic Heart Disease Risk Factor Study

Purpose N-6 polyunsaturated fatty acids (PUFA), particularly linoleic acid (LA), have been associated with lower risk of coronary heart disease (CHD), but little is known about their antiarrhythmic properties. We investigated the association of the serum n-6 PUFAs with the risk of atrial fibrillation (AF), the most common type of cardiac arrhythmia. Methods The study included 2450 men from the Kuopio Ischaemic Heart Disease Risk Factor Study, aged 42–60 years at baseline. The total n-6 PUFA includes linoleic acid (LA), arachidonic acid (AA), γ-linolenic acid (GLA) and dihomo-γ-linolenic acid (DGLA). Cox proportional hazards regression was used to estimate hazard ratio (HR) of incident events. Results During the mean follow-up of 22.4 years, 486 AF cases occurred. The multivariable-adjusted HR in the highest versus the lowest quartile of total serum n-6 PUFA concentration was 0.79 (95% CI 0.58–1.08, P trend = 0.04). When evaluated individually, only serum LA concentration was inversely associated with AF risk (multivariable-adjusted extreme-quartile HR 0.69, 95% CI 0.51–0.94, P trend = 0.02). These associations were stronger among the men without history of CHD or congestive heart failure at baseline, compared to men with such disease history (P for interaction = 0.05 for total n-6 PUFA and LA). Similar associations were observed with dietary LA and AA intakes. No significant associations were observed with serum AA, GLA or DGLA concentrations. Conclusions Higher circulating concentration and dietary intake of n-6 PUFA, mainly LA, are associated with lower risk of AF, especially among men without history of CHD or congestive heart failure.

Predicting COVID-19 Severity with a Specific Nucleocapsid Antibody plus Disease Risk Factor Score

ABSTRACT Effective methods for predicting COVID-19 disease trajectories are urgently needed. Here, enzyme-linked immunosorbent assay (ELISA) and coronavirus antigen microarray (COVAM) analysis mapped antibody epitopes in the plasma of COVID-19 patients (n = 86) experiencing a wide range of disease states. The experiments identified antibodies to a 21-residue epitope from nucleocapsid (termed Ep9) associated with severe disease, including admission to the intensive care unit (ICU), requirement for ventilators, or death. Importantly, anti-Ep9 antibodies can be detected within 6 days post-symptom onset and sometimes within 1 day. Furthermore, anti-Ep9 antibodies correlate with various comorbidities and hallmarks of immune hyperactivity. We introduce a simple-to-calculate, disease risk factor score to quantitate each patient’s comorbidities and age. For patients with anti-Ep9 antibodies, scores above 3.0 predict more severe disease outcomes with a 13.42 likelihood ratio (96.7% specificity). The results lay the groundwork for a new type of COVID-19 prognostic to allow early identification and triage of high-risk patients. Such information could guide more effective therapeutic intervention. IMPORTANCE The COVID-19 pandemic has resulted in over two million deaths worldwide. Despite efforts to fight the virus, the disease continues to overwhelm hospitals with severely ill patients. Diagnosis of COVID-19 is readily accomplished through a multitude of reliable testing platforms; however, prognostic prediction remains elusive. To this end, we identified a short epitope from the SARS-CoV-2 nucleocapsid protein and also a disease risk factor score based upon comorbidities and age. The presence of antibodies specifically binding to this epitope plus a score cutoff can predict severe COVID-19 outcomes with 96.7% specificity.

Bisphenol F exposure in adolescent heterogeneous stock (HS) rats affects growth and adiposity

Bisphenol F (BPF) is increasingly substituting bisphenol A (BPA) in manufacturing polycarbonates and consumer products. The cardiometabolic effects of BPF in either humans or model organisms are not clear, and no studies to date have investigated the role of genetic background on susceptibility to BPF-induced cardiometabolic traits. The primary goal of this project was to determine if BPF exposure influences growth and adiposity in male N: NIH Heterogeneous Stock (HS) rats, a genetically heterogeneous population. Littermate pairs of male HS rats were randomly exposed to either vehicle (0.1% Ethanol) or 1.125 µg/ml BPF in 0.1% Ethanol for five weeks in drinking water starting at three weeks-of-age. Water consumption and body weight was measured weekly, body composition was determined using nuclear magnetic resonance (NMR), urine and feces were collected in metabolic cages, and blood and tissues were collected at the end of the study. BPF-exposed rats showed significantly increased body growth and abdominal adiposity, risk factors for cardiometabolic disease. Urine output was increased in BPF-exposed rats, driving a trend in increased creatinine clearance. We also report the first relationship between a bisphenol metabolizing enzyme and a bisphenol-induced phenotype. Preliminary heritability estimates of significant phenotypes suggest that BPF exposure may alter trait variation. These findings support BPF exposure as a cardiometabolic disease risk factor and indicate that the HS rat will be a useful model for dissecting gene by BPF interactions on metabolic health.

Determinants of diabetes comorbidities in Indonesia: a cohort study of non-communicable disease risk factor

Background<br />Type 2 diabetes mellitus (DM) is a non-communicable disease that constitutes a huge health burden, with the presence of comorbidities of DM adding to it. This study aimed to obtain the main determinants of the combined incidence of DM and its main comorbidities in adults.<br /><br />Methods<br />This was a further analysis of the Non-Communicable Disease Risk Factor Cohort Study 2011 – 2018 involving 3730 subjects. Data of diabetes-free respondents at baseline were followed up every 2 years for 6 years. Data collection was carried out through interviews and health examinations. All subjects were assayed for blood glucose and lipid parameters. Chi-square test and Cox regression were implemented for data analysis.<br /><br />Results<br />During 6 years of follow-up, DM incidence occurred in 567 (15.2%) subjects. The most common comorbidities were increased low density lipoprotein (LDL), central obesity, increased total cholesterol, obesity and hypertension. Most of the comorbidities occurred before the diagnosis of DM incidence. The determinants of the combined DM incidence–increased LDL are obesity, hypertension, and a family history of DM. The determinants of the combined DM incidence–central obesity are increased triglycerides, hypertension, male gender, and family history of DM. While the determinants of the combined DM incidence–hypertension are obesity and increased triglycerides.<br /><br />CONCLUSION<br />This study demonstrated a high burden of diabetes incidence with comorbidities among adults. Knowledge of the magnitude of the diabetes<br />comorbidity determinants emphasizes the role of non pharmacological intervention such as weight reduction and dietary modification.