Background: Underlying mechanism leading to impaired lung function are incompletely understood. Objectives: To investigate whether protein profiling can provide novel insights into mechanisms leading to impaired lung function. Methods: We used four community-based studies (n = 2552) to investigate associations between 79 cardiovascular/inflammatory proteins and forced expiratory volume in 1 s percent predicted (FEV 1 %) assessed by spirometry. We divided the cohorts into discovery and replication samples and used risk factor-adjusted linear regression corrected for multiple comparison (false discovery rate of 5%). We performed Mendelian randomization analyses using genetic and spirometry data from the UK Biobank (n = 421,986) to assess causality. Measurements and main results: In cross-sectional analysis, 22 proteins were associated with lower FEV 1 % in both the discovery and replication sample, regardless of stratification by smoking status. The combined proteomic data cumulatively explained 5% of the variation in FEV 1 %. In longitudinal analyses (n = 681), higher plasma levels of growth differentiation factor 15 (GDF-15) and interleukin 6 (IL-6) predicted a more rapid 5-year decline in lung function (change in FEV 1 % per standard deviation of protein level − 1.4, (95% CI, − 2.5 to − 0.3) for GDF-15, and -0.8, (95% CI, − 1.5 to − 0.2) for IL-6. Mendelian randomization analysis in UK-biobank provided support for a causal effect of increased GDF-15 levels and reduced FEV 1 %. Conclusions: Our combined approach identified GDF-15 as a potential causal factor in the development of impaired lung function in the general population. These findings encourage additional studies evaluating the role of GDF-15 as a causal factor for impaired lung function.
Our findings suggest that even individuals with sub-clinical impairments of lung function in the community have concomitant endothelial dysfunction.
Background: Non-alcoholic fatty liver disease (NAFLD) is associated with dyslipidemia and increased cardiovascular disease risk. Dietary choices may produce profound effects on blood lipids. Thus, the purpose of this study was to investigate which foods modify blood lipids in NAFLD.Methods: Systematic review of published systematic reviews and randomized controlled trials (RCTs). Searches were performed in PubMed, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials, from inception through March 2020. Studies in populations with NAFLD, which provided data on foods or dietary patterns and blood lipids were included, but not weight loss diets, supplements, nor individual nutrients. The strength of evidence was evaluated using The Grading of Recommendations Assessment, Development, and Evaluation (GRADE).Results: No relevant systematic reviews were identified. Eleven RCTs were included in the qualitative synthesis. Two RCTs were included in meta-analyses, regarding the comparison between Mediterranean and Low-fat diets, in which there were no clear effects on either high-density lipoprotein cholesterol or triglycerides, with Low evidence. From single RCTs, there was Moderate evidence for reduced triglycerides by a healthy dietary pattern, compared with usual care; and for reduced total cholesterol by a probiotic yogurt, enriched with Lactobacillus acidophilus La5 and Bifidobacterium lactis Bb12, compared with conventional yogurt. For all other comparisons, the evidence was considered as Low or Very low.Conclusion: Few studies were identified which reported effects of foods on blood lipids in subjects with NAFLD. The possible beneficial effect of probiotics warrants further study. PROSPERO identifier: CRD42020178927.
Lifestyle management is the first line of treatment for moderately elevated blood lipids in healthy individuals. We investigated the effectiveness of providing food-based written advice for lowering low-density lipoprotein (LDL) cholesterol (intervention) or triglycerides (control) in a pragmatic randomized controlled trial with two parallel arms from 2018–2019 at a rural primary health care center. We sent feedback letters after 3 weeks and 6 months. Out of the 113 adult primary care patients randomized, 112 completed the study. There were no differences between the intervention and control groups for changes in LDL cholesterol after 3 weeks (mean ± standard deviation −0.21 ± 0.38 vs. −0.11 ± 0.34 mmol/L, p = 0.45) or 6 months (−0.05 ± 0.47 vs. 0.02 ± 0.41 mmol/L, p = 0.70) (primary outcome). Following the advice to consume plant sterols and turmeric was associated with a reduction in LDL cholesterol after 3 weeks. Following the advice to consume less carbohydrates was associated with reduced triglycerides. In the intervention arm, 14 individuals (25%) reduced their LDL cholesterol by ≥10% after three weeks. Their reduction was attenuated but maintained after six months (−7.1 ± 9.2% or −0.31 ± 0.38 mmol/L, p = 0.01 compared with baseline). They differed only in higher adherence to the advice regarding turmeric. In conclusion, this undemanding intervention had little effect on blood lipids for most individuals.
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