Bidirectional two-sample Mendelian randomization analysis identifies causal associations between cardiovascular diseases and frozen shoulder.

BACKGROUND: Although prior observational studies indicate an association between cardiovascular diseases (CVDs) and frozen shoulder (FS), the potential causal relationship between them remains uncertain. This study aims to explore the genetic causal relationship between CVDs and FS using Mendelian randomization (MR). METHODS: Genetic variations closely associated with FS were obtained from the FinnGen Consortium. Summary data for CVD, including atrial fibrillation (AF), coronary artery disease (CAD), heart failure (HF), myocardial infarction (MI), stroke, and ischemic stroke (IS), were sourced from several large-scale genome-wide association studies (GWAS). MR analysis was performed using inverse variance weighting (IVW), MR Egger, and weighted median methods. IVW, as the primary MR analysis method, complemented by other sensitivity analyses, was utilized to validate the robustness of the results. Further reverse MR analysis was conducted to explore the presence of reverse causal relationships. RESULTS: In the forward MR analysis, genetically determined risk of stroke and IS was positively associated with FS (OR [95% CI] = 1.58 (1.23-2.03), P < 0.01; OR [95% CI] = 1.46 (1.16-1.85), P < 0.01, respectively). There was no strong evidence of an effect of genetically predicted other CVDs on FS risk. Sensitivity analyses confirmed the robustness of the results. In the reverse MR analysis, no causal relationships were observed between FS and various CVDs. CONCLUSION: The study suggests that stroke increases the risk of developing FS. However, further basic and clinical research is needed to substantiate our findings.

The METS-IR is independently related to bone mineral density, FRAX score, and bone fracture among U.S. non-diabetic adults: a cross-sectional study based on NHANES.

AIM: The purpose of this study was to investigate the association between the metabolic score for insulin resistance (METS-IR) and bone mineral density (BMD) in American non-diabetic adults. METHODS: We conducted a cross-sectional study with 1114 non-diabetic adults from the National Health and Nutrition Examination Survey cycle (2013-2014). The associations between METS-IR and BMD of total femur and spine were assessed by the multiple linear regression and verified the non-linear relationship with a smooth curve fit and threshold effect model. Furthermore, we evaluated the relationship between METS-IR, FRAX score, and history of bone fractures. RESULTS: We found that BMD of the total femur and spine increased by 0.005 g/cm3 and 0.005 g/cm3, respectively, for a one-unit increase of METS-IR in all participants. This positive association was more pronounced among higher METS-IR participants, and there was a non-linear relationship, which was more significant when the MTTS-IRfemur was < 41.62 or the METS-IRspine was < 41.39 (ßfemur = 0.008, ßspine = 0.011, all P < 0.05). We also found that METS-IR was positively correlated with both FRAX scores in all female participants. However, METS-IR was positively correlated only with the 10-year hip fracture risk score in male participants with fractures. No significant association between METS-IR and a history of bone fractures. CONCLUSIONS: In American non-diabetic adults, there is a correlation between elevated levels of METS-IR within the lower range and increased BMD as well as decreased risk of fractures, suggesting that METS-IR holds promise as a novel biomarker for guiding osteoporosis (OP) prevention. However, it is important to carefully balance the potential benefits and risks of METS-IR in OP.