👤 Karl J Lackner

Elevated liver stiffness has been associated with atrial fibrillation (AFib) in the general population. The mechanism underlying this association is unclear. Participants were recruited from the general population and prospectively enrolled with follow-up for 5 years. The fibrosis-4 (FIB-4) index was used as a surrogate marker for liver fibrosis. Proteomics analysis was performed using the 92-target Olink inflammation panel. Validation was performed using the NAFLD fibrosis score (NFS), aspartate aminotransferase to platelet index (APRI), and repeat confirmation proteomics. A sample of 11,509 participants with a mean age of 54.0 ± 11.1 years, 51.3% women, and a median FIB-4 index of 0.85 (0.65/1.12), was used. The FIB-4 index was predictive for prevalent (FIB-4 index adjusted odds ratio (aOR) per SD: 1.100 with 95% CI 1.011-1.196; CXCL10 is linked to liver fibrosis, as determined by the FIB-4 index, and to prevalent AFib. How elevated liver stiffness relates to atrial fibrillation in the general population remains to be clarified. We hypothesized that systemic inflammation against a background of liver fibrosis produced from metabolic dysfunction-associated steatotic liver disease (MASLD), is involved in the pathophysiology of atrial fibrillation. Using large-scale targeted proteomics, we found that CXCL10 is related to both liver fibrosis, as defined by the fibrosis-4 index, and to atrial fibrillation. These results can aid evidence-based drug development for patients with atrial fibrillation and MASLD-related liver fibrosis. Show less

Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5−24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors. Show less

Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity. Show less

To identify genes and genetic markers associated with corneal astigmatism. A meta-analysis of genome-wide association studies (GWASs) of corneal astigmatism undertaken for 14 European ancestry (n=22,250) and 8 Asian ancestry (n=9,120) cohorts was performed by the Consortium for Refractive Error and Myopia. Cases were defined as having >0.75 diopters of corneal astigmatism. Subsequent gene-based and gene-set analyses of the meta-analyzed results of European ancestry cohorts were performed using VEGAS2 and MAGMA software. Additionally, estimates of single nucleotide polymorphism (SNP)-based heritability for corneal and refractive astigmatism and the spherical equivalent were calculated for Europeans using LD score regression. The meta-analysis of all cohorts identified a genome-wide significant locus near the platelet-derived growth factor receptor alpha ( In addition to replicating a previously identified genome-wide significant locus for corneal astigmatism near the Show less