BackgroundDyslipidemia is a major risk factor for cardiovascular events. The prognostic importance of lipoproteins in patients with atrial fibrillation is not well understood. We aimed to explore the association between apolipoprotein A1 (ApoA1) and B (ApoB) and cardiovascular events in patients with atrial fibrillation receiving oral anticoagulation.Methods and ResultsUsing data from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, ApoA1 and ApoB plasma levels were measured at baseline in 14 884 atrial fibrillation patients. Median length of follow‐up was 1.9 years. Relationships between continuous levels of ApoA1 and ApoB and clinical outcomes were evaluated using Cox models adjusted for cardiovascular risk factors, medication including statins, and cardiovascular biomarkers. A composite ischemic outcome (ischemic stroke, systemic embolism, myocardial infarction, and cardiovascular death) was used as the primary end point. Median (25th, 75th) ApoA1 and ApoB levels were 1.10 (0.93, 1.30) and 0.70 g/L (0.55, 0.85), respectively. In adjusted analyses, higher levels of ApoA1 were independently associated with a lower risk of the composite ischemic outcome (hazard ratio, 0.81; P<0.0001). Similar results were observed for the individual components of the composite outcome. ApoB was not significantly associated with the composite ischemic outcome (P=0.8240). Neither apolipoprotein was significantly associated with major bleeding. There was no interaction between lipoproteins and randomized treatment for the primary outcome (both P values ≥0.2448).ConclusionsIn patients with atrial fibrillation on oral anticoagulation, higher levels of ApoA1 were independently associated with lower risk of ischemic cardiovascular outcomes. Investigating therapies targeting dyslipidemia may thus be useful to improve cardiovascular outcomes in patients with atrial fibrillation.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

The mutualisms between fig trees and their pollinator fig wasps and between yucca plants and yucca moths are spectacular examples of coevolution. The characteristics of these independently evolved mutualisms have resulted from long‐term processes, the first stages of which are unknown. A fundamental question in the study of mutualism is how these interactions evolve. Seed predator/pollinator and host plant interactions, which may initially be considered as mainly antagonistic, have the potential to provide good model systems for the study of the first stages of evolution towards mutualism. We present here theoretical models assessing the consequences of interactions between specialized seed predator insects and their host plants. These models describe the parameters that affect the fitness of an individual female seed predator and her influence on the fitness of the host plant. In an optimal strategy for the seed predator, the number of eggs laid in each flower depends on the interaction between the adult and larva survival. Along with a growing predation pressure on adults and larvae several eggs must be laid in each flower by the female seed predator to enhance her fitness. However, in a situation where the host plant selectively aborts flowers with a high number of eggs the fitness of the seed predator will seriously decrease. If the cost of selective abortion is less than the cost of seed predation the host plant will maintain fitness. In a mutualistic relationship a balance between the cost and the benefit of the parameters in the fitness models of the seed predator and the host plant has to occur so that the net seed output is larger than zero (0). Any unselfish behaviour or quality of the seed predator that would benefit the host plant in such a way that the net seed output increases might be a first stage in an interaction becoming mutualistic. The models presented here will not only provide a platform for empirical studies on interactions that may swing from parasitism to mutualism, but also for seed predator/pollinator and host plant interactions in general.

ObjectiveWe investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes.MethodsA total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5–25  kg/m2; overweight, >25 to <30 kg/m2; and obese, ≥30 kg/m2. We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding.ResultsCompared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001).ConclusionsRegardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF.Trial registration numberNCT00412984.

Although several risk factors exist for acute coronary syndrome (ACS) no biomarkers for survival or risk of re-infarction have been validated. Previously, reduced serum concentrations of anti-ß1AR Ab have been implicated in poorer ACS outcomes. This study further evaluates the prognostic implications of anti-ß1AR-Ab levels at the time of ACS onset. Serum anti-ß1AR Ab concentrations were measured in randomly selected patients from within the PLATO cohort. Stratification was performed according to ACS event: ST-elevation myocardial infarct (STEMI) vs. non-ST elevation myocardial infarct (NSTEMI). Antibody concentrations at ACS presentation were compared to 12-month all-cause and cardiovascular mortality, as well as 12-month re-infarction. Sub-analysis, stratifying for age and the correlation between antibody concentration and conventional cardiac risk-factors was subsequently performed. Serum anti-ß1AR Ab concentrations were measured in 400/799 (50%) STEMI patients and 399 NSTEMI patients. Increasing anti-ß1AR Ab concentrations were associated with STEMI (p = 0.001). Across all ACS patients, no associations between anti-ß1AR Ab concentration and either all-cause cardiovascular death or myocardial re-infarction (p = 0.14) were evident. However among STEMI patients ≤60 years with anti-ß1AR Ab concentration <median higher rates of re-infarction were observed, compared to those with anti-ß1AR Ab concentrations > median (14/198 (7.1%) vs. 2/190 (1.1%)); p = 0.01). Similarly, the same sub-group demonstrated greater risk of cardiovascular death in year 1, including re-infarction and stroke (22/198 (11.1%) vs. 10/190 (5.3%); p = 0.017). ACS Patients ≤60 years, exhibiting lower concentrations of ß1AR Ab carry a greater risk for early re-infarction and cardiovascular death. Large, prospective studies quantitatively assessing the prognostic relevance of Anti-ß1AR Ab levels should be considered.

Aims Whether diabetes without insulin therapy is an independent cardiovascular (CV) risk factor in atrial fibrillation (AF) has recently been questioned. We investigated the prognostic relevance of diabetes with or without insulin treatment in patients in the ARISTOTLE trial. Methods and results Patients with AF and increased stroke risk randomized to apixaban vs. warfarin were classified according to diabetes status: no diabetes; diabetes on no diabetes medications; diabetes on non-insulin antidiabetic drugs only; or insulin-treated. The associations between such patient subgroups and stroke/systemic embolism (SE), myocardial infarction (MI), and CV death were examined by Cox proportional hazard regression, both unadjusted and adjusted for other prognostic variables. Patients with diabetes were younger and had a higher body mass index. Median CHA2DS2VASc score was 4.0 in patients with diabetes and 3.0 in patients without diabetes. We found no significant difference in stroke/SE incidence across patient subgroups. Compared with no diabetes, only insulin-treated diabetes was significantly associated with higher risk. When adjusted for clinical variables, compared with no diabetes, the hazard ratios (HRs) for MI (95% confidence intervals) were for diabetes on no medication: 1.15 (0.62–2.14); for diabetes on non-insulin antidiabetic drugs: 1.32 (0.90–1.94); for insulin-treated diabetes: 2.34 (1.43–3.82); interaction P = 0.008. HRs for CV death were for diabetes on no medication: 1.19 (0.86–166); for diabetes on non-insulin antidiabetic drugs: 1.12 (0.88–1.42); for insulin-treated diabetes 1.85 (1.36–2.53), interaction P = 0.001. Conclusion In anticoagulated patients with AF, a higher risk of MI and CV death is largely confined to diabetes treated with insulin.