Association of Life’s Essential 8 and Genetic Predisposition with the Risk of Osteoarthritis: A Prospective Cohort Study

Changyu Du¹Tingting Zhou¹Xiang Ji^2,3Xiaofu Tang⁴Honghao Yang³Zheng Ma³Mingjie Kuang⁴Liangkai Chen⁵Xiaofeng Li²Hongfei Wang¹Chengrui Yang⁶Xiaoming Li¹Jianyong Zhao¹Yang Xia^2,3*

• ¹Cangzhou Integrated Traditional Chinese and Western Medicine Hospital, Cangzhou, China
• ²Shenyang Medical College, Shenyang, China
• ³Shengjing Hospital of China Medical University, Shenyang, China
• ⁴Central Hospital Affiliated to Shandong First Medical University, Jinan, China
• ⁵Huazhong University of Science and Technology Tongji Medical College, Wuhan, China
• ⁶Hebei University of Chinese Medicine, Shijiazhuang, China

Background: Osteoarthritis is a prevalent joint disorder with significant health and economic impacts. While individual CVH factors have been linked to OA, a comprehensive understanding of how overall CVH influences OA risk is lacking. LE8 offers a holistic measure incorporating physical activity, body mass index, diet, sleep, blood pressure, blood sugar, lipids, and nicotine exposure. The inclusion of LE8 in OA research is crucial to better understand the broader CVH-OA association. Methods: The present study was conducted using data from the UK-Biobank, which initially included more than 500,000 participants. After applying exclusion criteria, a total of 242,278 participants without hip and/or knee OA at baseline were included in the final analyses. Genetic risk scores for hip, knee, and hip/knee OA were derived from 70, 83, and 87 single-nucleotide polymorphisms, respectively. Restricted cubic splines (RCS) were utilized to explore the potential non-linear associations of GRSs with the risks of OA. Cox proportional hazards models were applied to assess the associations between LE8, GRSs, and the risk of OA. Both combined effect and interaction analyses were conducted to evaluate how LE8 and GRSs jointly influence OA risk. Results: During a median follow-up period of 12.12 years, 18,767 participants developed hip and/or knee OA. LE8 was found to be negatively associated with the risks of hip, knee, and hip/knee OA. CVH, as measured by LE8 scores, was categorized into three groups based on the following boundary values: high CVH (80–100 points), moderate CVH (50–79 points), and low CVH (0–49 points). Compared to the participants with low CVH, the HRs (95% CIs) of hip, knee, and hip/knee OA for those with high CVH were 0.71 (0.64, 0.79), 0.48 (0.44, 0.52), and 0.56 (0.52, 0.60), respectively. These associations were not modified by GRSs. In the joint association analyses, the lowest HR (hip OA: 0.48, 0.41-0.55; knee OA: 0.34, 0.30-0.39; hip/knee OA: 0.43, 0.39-0.47) of events were observed in those with both high CVH and low GRSs, compared to those low CVH and high GRSs. Conclusion: Our findings underscore the importance of maintaining the maximum CVH to prevent the onset of OA, irrespective of genetic predisposition.