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This document is a list of references and sources related to the topic of inferring causation from observational studies in the vision sciences. It includes articles and resources from various sources, such as scientific journals and research projects. The topics covered include genetic findings in the UK Biobank, Mendelian randomization, body composition measurement, and the relationship between muscle strength and various health factors. The document also includes information on cholesterol levels, lipoproteins, and their association with cardiovascular disease. [Extracted from the article]

Abstract Background Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis Dogs with B. canis‐induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals Twenty‐nine client‐owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods Observational cross‐sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA‐1 (radioimmunoassay) and SAA was determined. Results Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1‐716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0‐4.2 μg/mL) (P

Aims: Reduced muscle mass and reduced strength are frequently associated with both alterations in blood lipids and poorer cardiometabolic outcomes in epidemiological studies; however, a causal association cannot be determined from such observations. Two-sample Mendelian randomization (MR) was applied to assess the association of genetically determined appendicular lean mass (ALM) and handgrip strength (HGS) with serum lipid particle diameter., Methods and Results: Mendelian randomization was implemented using summary-level data from the largest genome-wide association studies on ALM ( n = 450 243), HGS ( n = 223 315), and lipoprotein [low-density lipoprotein (LDL), very LDL (VLDL), and high-density lipoprotein (HDL)] particle diameters ( n = 115 078). Inverse variance-weighted (IVW) method was used to calculate the causal estimates. Weighted median-based method, MR-Egger, and leave-one-out method were applied as sensitivity analysis. Greater ALM had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.055, SE = 0.031, P = 0.081; IVW: β = 0.068, SE = 0.014, P < 0.001) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.114, SE = 0.039, P = 0.003; IVW: β = -0.081, SE = 0.017, P < 0.001). Similarly, greater HGS had a statistically significant positive effect on HDL particle diameter (MR-Egger: β = 0.433, SE = 0.184, P = 0.019; IVW: β = 0.121, SE = 0.052, P = 0.021) and a statistically significant negative effect on VLDL particle diameter (MR-Egger: β = -0.416, SE = 0.163, P = 0.011; IVW: β = -0.122, SE = 0.046, P = 0.009). There was no statistically significant effect of either ALM or HGS on LDL particle diameter., Conclusion: There were potentially causal associations between both increasing ALM and HGS and increasing HDL particle size and decreasing VLDL particle size. These causal associations may offer possibilities for interventions aimed at improving cardiovascular disease risk profile., Competing Interests: Conflict of interest: R.K. has received payments from Abbott for the creation of educational media content, as well as speaker fees. All other authors declare that they have no relevant conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Babesia canis infection induces a marked acute phase response (APR) that might be associated with alteration in lipid and lipoprotein metabolism and disease prognosis. Hypothesis: Dogs with B. canis‐induced APR develop dyslipidemia with altered lipoprotein concentration and morphology. Animals: Twenty‐nine client‐owned dogs with acute B. canis infection and 10 clinically healthy control dogs. Methods: Observational cross‐sectional study. Serum amyloid A (SAA) was measured using ELISA. Cholesterol, phospholipids, and triglycerides were determined biochemically. Lipoproteins were separated using agarose gel electrophoresis. Lipoprotein diameter was assessed by polyacrylamide gradient gel electrophoresis; correlation with ApoA‐1 (radioimmunoassay) and SAA was determined. Results: Dogs with B. canis infection had a marked APR (median SAA, 168.3 μg/mL; range, 98.1‐716.2 μg/mL) compared with controls (3.2 μg/mL, 2.0‐4.2 μg/mL) (P < .001). Dogs with B. canis infection had significantly lower median cholesterol (4.79 mmol/L, 1.89‐7.64 mmol/L versus 6.15 mmol/L, 4.2‐7.4 mmol/L) (P =.02), phospholipid (4.64 mmol/L, 2.6‐6.6 mmol/L versus 5.72 mmol/L, 4.68‐7.0 mmol/L) (P =.02), and α‐lipoproteins (77.5%, 27.7%‐93.5% versus 89.2%, 75.1%‐93.5%) (P =.04), and higher ApoA‐1 (1.36 U, 0.8‐2.56 U versus 0.95 U, 0.73‐1.54 U) concentrations (P =.02). Serum amyloid A correlated with high‐density lipoproteins (HDLs) diameter (rho =.43; P =.03) and ApoA‐1 (rho =.63, P < .001). Conclusions and Clinical Importance: Major changes associated with B. canis‐induced APR in dogs are related to concentration, composition, and morphology of HDL particles pointing to an altered reverse cholesterol transport. Parallel ApoA‐1 and SAA concentration increase is a unique still unexplained pathophysiological finding. [ABSTRACT FROM AUTHOR]

Lipoprotein subfractions help discriminate cardiometabolic disease risk. Genetic loci validated as associating with lipoprotein measures do not account for a large proportion of the individual variation in lipoprotein measures. We hypothesized that DNA methylation levels across the genome contribute to interindividual variation in lipoprotein measures. Using data from participants of the Genetics of Lipid Lowering Drugs and Diet Network (n = 663 for discovery and n = 331 for replication stages, respectively), we conducted the first systematic screen of the genome to determine associations between methylation status at ∼470,000 cytosine-guanine dinucleotide (CpG) sites in CD4+ T cells and 14 lipoprotein subfraction measures. We modeled associations between methylation at each CpG site and each lipoprotein measure separately using linear mixed models, adjusted for age, sex, study site, cell purity, and family structure. We identified two CpGs, both in the carnitine palmitoyltransferase-1A (CPT1A) gene, which reached significant levels of association with VLDL and LDL subfraction parameters in both discovery and replication phases (P < 1.1 × 10−7 in the discovery phase, P < .004 in the replication phase, and P < 1.1 × 10−12 in the full sample). CPT1A is regulated by PPARα, a ligand for drugs used to reduce CVD. Our associations between methylation in CPT1A and lipoprotein measures highlight the epigenetic role of this gene in metabolic dysfunction.

Introduction. In recent years, cholesterol has received interest in the study of infection due to evidence of a relationship between low plasma cholesterol levels and tuberculosis (TB). Hypothesis/Gap Statement. Plasma lipid profiles of serum amyloid A (SAA), apolipoprotein A-I and high-density lipoprotein cholesterol (HDL-C) are biomarkers associated with symptomatic TB patients. Objective. We aimed to evaluate plasma lipid profiles of apolipoprotein A-I, SAA and the size of HDL as biomarkers to diagnose symptomatic TB patients. Methodology. Patients with TB symptoms attending the Instituto Brasileiro para a Investigação da Tuberculose/Fundação José Silveira (IBIT/FJS) between September 2015 and August 2016 for diagnosis of TB were studied. From 129 patients, 97 were classified as pulmonary TB and 32 as negative-bacilloscopy (non-TB group). Medical history, fasting serum and plasma were obtained. Total cholesterol (TC), HDL-C, apolipoprotein A-I and SAA were measured by enzymatic or immunochemical reaction assays. HDL size was measured by laser light-scattering. Results. In TB patients, TC (147.0±37 vs. 168±44 mg dL -1 ), HDL-C (37±14 vs. 55±18 mg dL -1 ) and apolipoprotein A-I (102±41 vs. 156±47 mg dL -1 ) concentrations were lower ( P <0.0001), while HDL particle size (10.16±1.02 vs. 9.62±0.67 nm) and SAA levels (280±36 vs. 19±8 mg L -1 ) were higher ( P <0.0001). Using receiver-operating characteristic curve analysis for predicting TB, the cutoff values were <83.85 mg L -1 for SAA (sensitivity=96.88 %, specificity=78.43 %, P <0.0001), >44.50 mg dL -1 for HDL-C (sensitivity=75 %, specificity=72.16 %, P <0.001) and >118.5 mg dL -1 for apolipoprotein A-I (sensitivity=83.83 %, specificity=72.22 %, P <0.001). Conclusion. SAA, HDL-C and apolipoprotein A-I are associated with TB infection and could be used as laboratory biomarkers, especially in patients who are negative for alcohol-acid-resistant bacilli.

A shift towards overall larger very low-density lipoprotein (VLDL), and smaller low-density lipoprotein and high-density lipoprotein (HDL) diameters occurs in insulin resistance (IR), which reflects shifts in the distribution of the subfraction concentrations. Fenofibrate, indicated for hypertriglyceridemia, simultaneously reduces IR and shifts in lipoprotein diameter. Individual responses to fenofibrate vary, and we conducted a genome-wide association study to identify genetic differences that could contribute to such differences.Association analysis was conducted between single nucleotide polymorphisms (SNPs) on the Affymetrix 6.0 array and fasting particle diameter responses to a 12-week fenofibrate trial, in 817 related Caucasian participants of the Genetics of Lipid Lowering Drugs and Diet Network. Linear models were conducted, which adjusted for age, sex and study center as fixed effects, and pedigree as a random effect. The top three SNPs associated with each fraction were examined subsequently for associations with changes in subfraction concentrations.SNPs in AHCYL2 and CD36 genes reached, or closely approached, genome-wide levels of significance with VLDL and HDL diameter responses to fenofibrate, respectively (P=4×10-9 and 8×10-8). SNPs in AHCYL2 were associated with a decrease in the concentration of the large VLDL subfraction only (P=0.002). SNPs associated with HDL diameter change were not associated with a single subfraction concentration change (P>0.05) indicating small shifts across all subfractions.We report novel associations between lipoprotein diameter responses to fenofibrate and the AHCYL2 and CD36 genes. Previous associations of these genes with IR emphasize the role of IR in mediating lipoprotein response to fenofibrate. [ABSTRACT FROM AUTHOR]

Transvascular lipoprotein transport in patients with chronic renal disease. Background. While increased plasma cholesterol is a well-established cardiovascular risk factor in the general population, this is not so among patients with chronic renal disease. We hypothesized that the transvascular lipoprotein transport, in addition to the lipoprotein concentration in plasma, determines the degree of atherosclerosis among patients with chronic renal disease. Methods. We used an in vivo method for measurement of transvascular transport of low-density lipoprotein (LDL) in 21 patients with chronic renal disease and in 42 healthy control patients. Autologous 131-iodinated LDL was reinjected intravenously, and the 1-hour fractional escape rate was taken as index of transvascular transport. Results. Transvascular LDL transport tended to be lower in patients with chronic renal disease than in healthy control patients [3.3 (95% CI 2.4–4.2) vs. 4.2 (3.7–4.2)%/hour; NS]. However, this tendency disappeared when transvascular LDL transport was corrected for distribution volume of LDL [1.7 (1.2–2.2) vs. 1.8 (1.6–2.0) %/(hour × (L/m2)); NS]. There was significant variation in transvascular LDL transport between diabetic patients with chronic renal disease, nondiabetic patients with chronic renal disease, and healthy control patients [5.0 (3.2–7.8) vs. 3.0 (2.2–3.8) vs. 4.2 (3.6–4.8) %/hour; P < 0.01 after adjustment for distribution volume of LDL]. This variation was unlikely caused by altered hepatic LDL receptor expression or glycosylation of LDL in diabetes patients. Conclusion. Transvascular LDL transport may be increased in diabetic patients with chronic renal disease, suggesting that lipoprotein flux into the arterial wall is increased. A similar mechanism does not operate in nondiabetic patients with chronic renal disease. [ABSTRACT FROM AUTHOR]