Ideal cardiovascular health metrics have better identification of arthritis
理想的心血管健康指标能更好地识别关节炎

Abstract 摘要

Introduction 导言

Arthritis (AR) means inflammation or swelling of one or more joints [1], mainly including osteoarthritis (OA) and rheumatoid arthritis (RA). AR could cause pain and limited mobility in the joints [1, 2], as well as extra-articular manifestations such as rheumatoid nodules, other systemic involvement, and systemic comorbidities [3]. An estimated 58.5 million U.S. adults (22.7%) were told by their doctors each year from 2013 to 2015 that they had some form of AR [4]. According to relevant studies, the prevalence of AR and the limitation of activities caused by it will increase significantly by 2030 [5]. As a major public health problem, AR had brought a heavy medical and economic burden.
关节炎（AR）是指一个或多个关节的炎症或肿胀[ 1]，主要包括骨关节炎（OA）和类风湿性关节炎（RA）。AR可引起关节疼痛和活动受限[1, 2]，也可引起关节外表现，如类风湿结节、其他系统受累和全身合并症[3]。据估计，2013 年至 2015 年期间，每年有 5850 万美国成年人（22.7%）被医生告知患有某种形式的 AR [ 4]。根据相关研究，到 2030 年，AR 的患病率及其造成的活动限制将显著增加[5]。作为一个重大的公共卫生问题，AR 带来了沉重的医疗和经济负担。

The American Heart Association (AHA) proposed the concept of ICVHM, which was based on seven health metrics [6]. Previous studies had confirmed the association between ICVHM and cardiovascular disease (CVD) [7, 8]. AR and CVD share risk factors as well as biological and behavioral mechanisms [9–11].
美国心脏协会（AHA）提出了基于七项健康指标的 ICVHM 概念[6]。先前的研究证实了 ICVHM 与心血管疾病（CVD）之间的联系[7, 8]。AR 和心血管疾病具有相同的风险因素以及生物和行为机制[9- 11]。

Previous studies have pointed out that some indicators in ICVHM were associated with AR. Senbo Zhu et al [12] and Milena A. Gianfrancesco et al [13] studied the relationship between smoking with OA and RA, respectively. A review confirms that arthritis-induced pain can be relieved by physical activity [14]. Sally Thomas et al. provide evidence of a role in osteoarthritis through diet [15]. Karen Ching et al [16] suggested a strong association between hypertension and arthritis and raised the possibility of using anti-hypertensive drugs to treat osteoarthritis. However, there is still no comprehensive index to clarify the association of these single indicators with AR. Fortunately, ICVHM is a comprehensive indicator that includes multiple factors (smoking, diet, physical activity, BMI, blood pressure, blood glucose, and total cholesterol) [6]. Thus, we used ICVHM to investigate their association and the possibility of identifying AR. We hypothesized that there is an association between ICVHM and AR, and that ICVHM may better identify AR. Therefore, this study aimed to explore the relationship between AR (and its different types) and ICVHM, as well as the interactions of various indicators in ICVHM on AR in US adults.
以往的研究指出，ICVHM中的一些指标与AR相关。Senbo Zhu 等人[ 12] 和 Milena A. Gianfrancesco 等人[ 13] 分别研究了吸烟与 OA 和 RA 的关系。一篇综述证实，体育锻炼可缓解关节炎引起的疼痛[14]。莎莉-托马斯等人提供了通过饮食在骨关节炎中发挥作用的证据[ 15]。Karen Ching 等人[ 16] 认为高血压与关节炎之间存在密切联系，并提出了使用抗高血压药物治疗骨关节炎的可能性。然而，目前仍没有一个全面的指标来阐明这些单一指标与 AR 的关系。幸运的是，ICVHM 是一个包括多种因素（吸烟、饮食、体力活动、体重指数、血压、血糖和总胆固醇）的综合指标[6]。因此，我们使用 ICVHM 来研究它们之间的关联以及识别 AR 的可能性。我们假设 ICVHM 与 AR 之间存在关联，并且 ICVHM 可以更好地识别 AR。因此，本研究旨在探讨美国成年人中的 AR（及其不同类型）与 ICVHM 之间的关系，以及 ICVHM 中的各种指标对 AR 的交互作用。

Materials and methods 材料和方法

Results 成果

Table 1 showed the background characteristics and the prevalence of AR in adult respondents. Among 17,041 participants, 4566 (26.4%) had AR. In addition, participants with ICVHM scores ≤ 1, 2, 3, 4, and ≥ 5 accounted for 15.2%, 19.2%, 23.0%, 19.0%, and 23.6%, respectively. The distribution of age, gender, race, and education was significantly different between AR patients and non-AR participants, as well as between different ICVHM score groups (P < 0.001).
表 1 显示了成年受访者的背景特征和 AR 患病率。在 17 041 名参与者中，有 4566 人（26.4%）患有 AR。此外，ICVHM 分数≤ 1、2、3、4 和≥ 5 的受访者分别占 15.2%、19.2%、23.0%、19.0% 和 23.6%。年龄、性别、种族和教育程度的分布在 AR 患者和非 AR 参与者之间以及不同 ICVHM 评分组之间存在显著差异（P < 0.001）。

We used multivariate logistic regression analysis to explore the effects of seven independent health factors and ICVHM scores, and the results were shown in Table 2. Compared to the unhealthy groups, the ORs in the health status of smoking, physical activity, BMI, blood pressure, blood glucose, and total cholesterol were 0.598, 0.603, 0.479, 0.348, 0.441, and 0.491, respectively. Figure 1 shows the area under the curve (AUC) values for ICVHM and its parameters in the identification of AR. ICVHM as a composite has a maximum AUC value of 0.765, which is higher than the AUC value of the individual indicators.
我们使用多变量逻辑回归分析来探讨七个独立健康因素和 ICVHM 评分的影响，结果如表 2 所示。与不健康组相比，吸烟、体力活动、体重指数、血压、血糖和总胆固醇等健康状况的 OR 分别为 0.598、0.603、0.479、0.348、0.441 和 0.491。图 1 显示了 ICVHM 及其参数在识别 AR 时的曲线下面积（AUC）值。ICVHM 作为一个综合指标的最大 AUC 值为 0.765，高于单个指标的 AUC 值。

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Fig. 1 图 1

Area under the curve values for ICVHM and its parameters in the identification of AR
用于识别 AR 的 ICVHM 及其参数的曲线下面积值

And compared to participants who “≤ 1” score, the ORs of AR in participants with 2, 3, 4, and ≥ 5 for AR according to ICVHM scores were 0.586, 0.472, 0.259, and 0.130, respectively. In subgroup analysis, compared with participants with ≤ 1 score, the ORs of AR in the age ≤ 65 and > 65 years old were 0.097 and 0.434 who met ≥ 5 score. In the male and female groups, compared with participants with ≤ 1 score, the ORs of participants with ≥ 5 score were 0.208, and 0.100, respectively. Similar results were observed in subgroups stratified by race, marital status, education, ratio of family income to poverty (PIR), and drinking (Table 3). In addition, we also found ICVHM had interaction effects between age, gender, race, and ICVHM on AR (P < 0.05). In the age ≤ 65 years old group, the protective effect of ICVHM on AR was relatively stronger than in the elderly. Similarly, the OR was generally smaller in females than that in males. Compared to non-Hispanic whites, ICVHM had a stronger protective effect on AR in other races.
而与"≤1 "分的参与者相比，根据ICVHM评分，AR为2、3、4和≥5分的参与者的AR OR分别为0.586、0.472、0.259和0.130。在亚组分析中，与得分≤1分的参与者相比，年龄≤65岁和大于65岁的参与者中，得分≥5分者AR的OR值分别为0.097和0.434。在男性组和女性组中，与得分≤1分的参与者相比，得分≥5分的参与者的OR值分别为0.208和0.100。在按种族、婚姻状况、教育程度、家庭收入与贫困比例（PIR）和饮酒情况分层的亚组中也观察到类似的结果（表 3）。此外，我们还发现年龄、性别、种族和 ICVHM 对 AR 有交互影响（P < 0.05）。在年龄小于 65 岁的人群中，ICVHM 对 AR 的保护作用相对强于老年人。同样，女性的OR值普遍小于男性。与非西班牙裔白人相比，ICVHM 对其他种族的 AR 有更强的保护作用。

We further analyzed the relationship between ICVHM scores and different types of AR and made the results more intuitive by plotting the forest plot (Figure S2). Whether it was OA, RA, or Other AR, the P-trend of ICVHM scores was < 0.001, and compared with ICVHM score ≤ 1, the ORs of ≥ 5 were 0.174, 0.224, and 0.188, respectively.
我们进一步分析了ICVHM评分与不同类型AR之间的关系，并通过绘制森林图（图S2）使结果更加直观。无论是OA、RA还是其他AR，ICVHM评分的P趋势均<0.001，与ICVHM评分≤1相比，≥5的OR值分别为0.174、0.224和0.188。

Our study also explored the association between ICVHM and different types of AR in different characteristic populations, the results of the logistic analysis were shown in Table 4. In the age > 65 years old, the OR of the association between OA and ICVHM was 0.874, slightly higher than 0.649 in the age ≤ 65 years old. And in different genders, their associations were still significant (all P values were < 0.001). The association between RA and ICVHM was significant in the age ≤ 65 years old (P < 0.001), but not in the age > 65 years old (P = 0.956). And the ORs in the males and females were 0.770 and 0.730, respectively. For Other AR, in the males and females, the ORs were 0.733 and 0.689, as well as in the age ≤ 65 and > 65 years old, the ORs were 0.699 and 0.726, respectively. There were interaction effects between ICVHM and age for both OA and RA, and only interaction between race and ICVHM on OA.
我们的研究还探讨了不同特征人群中 ICVHM 与不同类型 AR 之间的关系，逻辑分析结果如表 4 所示。在年龄大于 65 岁的人群中，OA 与 ICVHM 的相关性 OR 为 0.874，略高于年龄小于 65 岁人群的 0.649。在不同性别中，二者的相关性仍然显著（所有 P 值均小于 0.001）。RA 与 ICVHM 的关系在年龄小于 65 岁时显著（P < 0.001），但在年龄大于 65 岁时不显著（P = 0.956）。男性和女性的 OR 分别为 0.770 和 0.730。在其他 AR 方面，男性和女性的 OR 值分别为 0.733 和 0.689，年龄小于 65 岁和大于 65 岁的 OR 值分别为 0.699 和 0.726。对于 OA 和 RA，ICVHM 与年龄之间存在交互效应，而对于 OA，种族与 ICVHM 之间仅存在交互效应。

The interaction diagram between variables is shown in Figure S3 and Table S2 in the supplement. We observed that there is an interaction between each indicator, and the strongest interaction is blood pressure and total cholesterol (0.43), followed by blood pressure and blood glucose (0.34), BMI and blood pressure (0.32), etc.
变量之间的交互作用图见图 S3 和补编中的表 S2。我们观察到各指标之间存在交互作用，其中交互作用最强的是血压与总胆固醇（0.43），其次是血压与血糖（0.34）、体重指数与血压（0.32）等。

Discussion 讨论

In this cross-sectional study, which included 17,041 U.S. adults, we found a high prevalence of AR of 26.8% and a negative association between ICVHM scores and the prevalence of AR, including OA, RA and other AR. ICVHM has the highest AUC value when compared to a single indicator. There were interactions between age, gender, race, and ICVHM on AR. These observations suggest an association between ICVHM and AR, with better identification of AR compared to a single indicator.
在这项包括 17,041 名美国成年人的横断面研究中，我们发现 AR 的患病率高达 26.8%，而 ICVHM 评分与包括 OA、RA 和其他 AR 在内的 AR 患病率呈负相关。与单一指标相比，ICVHM 的 AUC 值最高。年龄、性别、种族和 ICVHM 对 AR 的影响存在交互作用。这些观察结果表明，ICVHM 与 AR 之间存在关联，与单一指标相比，ICVHM 能更好地识别 AR。

In this study, we found that smoking, physical activity, BMI, blood pressure, blood glucose, and total cholesterol were independently and negatively associated with AR among the single variables constituting ICVHM. These indicators may influence the development and progression of arthritis through potential mechanisms. Similar to previous studies, the study of Sugiyama et al [26], smoking had been reported to be associated with an increased risk of RA, which may be related to the formation of citrullination of antigens and the formation of anti-citrullinated peptide antibodies (ACPAs) in RA [27, 28]. There was clear evidence that physical activity was associated with a variety of diseases, and physical activity had also been recommended for a healthy population and AR patients [29, 30]. In our research, the same results have been obtained. In a Swiss study, obese participants had higher rates of AR and significantly more pain than non-obese participants, which may be related to less physical activity in the obese population [31]. There was a strong association between high blood pressure and AR, and it was also common comorbidity of AR [16, 32, 33], which may be related to higher concentrations of homocysteine and leptin [34], but the specific mechanism needs to be further studied. Our study also confirmed the association between blood glucose and AR, and the meta-analysis by Karin et al [35]and Hui Pi et al [36], highlighted the association of glucose metabolism with OA and RA. However, in the study of Lusen et al [37], the opposite view was proposed, suggesting that the association between AR and blood glucose may be due to the presence of confounding factors such as obesity. Similarly, our findings support the association between total cholesterol and AR [38]. In this study, no independent association between diet and AR was found. However, different from our results, a clinical trial proved that diet was better than exercise alone in relieving AR symptoms [39], Sajedeh Jandari et al [40] demonstrated the association of the dietary inflammatory index(DII) and HEI with RA in their study, which may be related to the inconsistent relationship between AR and different nutrients in the diet [41], and the inconsistent grouping of the healthy diet. Meanwhile, ICVHM, as a comprehensive indicator, can better identify AR, which proves that better results can be achieved by applying ICVHM to prevent and identify AR.
在本研究中，我们发现在构成 ICVHM 的单一变量中，吸烟、体力活动、体重指数、血压、血糖和总胆固醇与 AR 呈独立负相关。这些指标可能通过潜在的机制影响关节炎的发生和发展。与之前的研究类似，Sugiyama 等人的研究[26]也报道了吸烟与 RA 风险增加有关，这可能与 RA 中抗原瓜氨酸化的形成和抗瓜氨酸肽抗体（ACPA）的形成有关[27, 28]。有明确的证据表明，体育锻炼与多种疾病相关，而且体育锻炼也被推荐给健康人群和AR患者[29，30]。我们的研究也取得了同样的结果。在瑞士的一项研究中，与非肥胖参与者相比，肥胖参与者的 AR 患病率更高，疼痛感也明显更强，这可能与肥胖人群运动量较少有关[31]。高血压与 AR 有密切关系，也是 AR 的常见合并症[16, 32, 33]，这可能与同型半胱氨酸和瘦素浓度较高有关[34]，但具体机制有待进一步研究。我们的研究也证实了血糖与 AR 的关系，Karin 等[35]和 Hui Pi 等[36]的荟萃分析也强调了糖代谢与 OA 和 RA 的关系。然而，Lusen 等人[ 37] 的研究提出了相反的观点，认为 AR 与血糖之间的关联可能是由于肥胖等混杂因素的存在。 同样，我们的研究结果也支持总胆固醇与 AR 之间的关系[38]。在这项研究中，没有发现饮食与 AR 之间的独立关联。然而，与我们的研究结果不同的是，一项临床试验证明，饮食在缓解 AR 症状方面优于单纯运动[39]，Sajedeh Jandari 等人[40]的研究表明，膳食炎症指数（DII）和 HEI 与 RA 存在关联，这可能与 AR 与膳食中不同营养素之间的关系不一致[41]，以及健康膳食的分组不一致有关。同时，ICVHM 作为一个综合指标，能更好地识别 AR，这证明应用 ICVHM 预防和识别 AR 能取得更好的效果。

In subgroup analyses, we observed a trend association between ICVHM scores and AR, the P value for the trend was < 0.001 for each subgroup, and we found interactions between ICVHM scores and age, gender, and race. The OR of AR was higher in the age ≤ 65 years old than the elderly, especially in participants with ICVHM score ≥ 5, which indicated that ICVHM was more closely related to AR in the non-elderly population, and it suggested the importance of early prevention of AR. Previous researches had shown that females were more susceptible to the impact of AR [42, 43]. In females, ICVHM scores were more associated with AR than in males, possibly due to differences in genetics and sex hormone secretion affecting the development and activity of the immune system [44], as well as the effect of hormones on structural changes in bones and joints [45]. The finding provided important implications for AR prevention among the specific population of females. Similarly, the association of ICVHM scores with AR was stronger in other race group than in non-Hispanic whites, which may be influenced by social status, health insurance, lifestyle, and other factors [46]. This study provided new ideas for further research on the association between ICVHM scores and AR in different demographic characteristics.
在亚组分析中，我们观察到ICVHM评分与AR之间存在趋势性关联，每个亚组的趋势性P值均小于0.001，并且我们发现ICVHM评分与年龄、性别和种族之间存在交互作用。年龄≤65岁人群的AR OR高于老年人，尤其是ICVHM评分≥5分的人群，这表明ICVHM与非老年人群的AR关系更为密切，提示了早期预防AR的重要性。以往的研究表明，女性更容易受到 AR 的影响[42, 43]。与男性相比，女性的 ICVHM 评分与 AR 的相关性更高，这可能是由于遗传和性激素分泌的差异影响了免疫系统的发育和活性[44]，以及激素对骨骼和关节结构变化的影响[45]。这一发现为在特定女性人群中预防 AR 提供了重要启示。同样，与非西班牙裔白人相比，其他种族群体的 ICVHM 评分与 AR 的关联性更强，这可能受到社会地位、医疗保险、生活方式和其他因素的影响[46]。这项研究为进一步研究不同人口特征的 ICVHM 评分与 AR 之间的关系提供了新思路。

We analyzed the association between ICVHM scores and different types of AR and found that different types of AR were negatively correlated with the score of ICVHM and the trend test was meaningful in each subgroup. As mentioned above, this may be related to the influence of multiple indicators in ICVHM on AR [26–33, 35, 36, 38]. Therefore, our findings suggested that higher ICVHM scores may be valuable for preventing AR and its different types. In addition, among the different ICVHM indicators, blood pressure and total cholesterol, blood pressure and blood glucose, BMI and blood pressure have a strong correlation, and by controlling the more strongly correlated indicators, multiple aspects can be controlled simultaneously, which provides a new idea for the prevention of arthritis in the future.
我们分析了 ICVHM 评分与不同类型 AR 之间的关联，发现不同类型的 AR 与 ICVHM 评分呈负相关，且趋势检验在每个亚组中都有意义。如上所述，这可能与 ICVHM 中多个指标对 AR 的影响有关[26- 33, 35, 36, 38]。因此，我们的研究结果表明，较高的 ICVHM 分数可能对预防 AR 及其不同类型有价值。此外，在不同的ICVHM指标中，血压与总胆固醇、血压与血糖、体重指数与血压具有较强的相关性，通过控制相关性较强的指标，可以同时控制多个方面，为今后预防关节炎提供了新的思路。

Strengths of the current study include that NHANES was able to ensure the validity of the data because it used strict quality assurance procedures when conducting surveys and had a large representative sample that could be extrapolated to all adults in the U.S. through weighted analysis. The cardiovascular-related indicators used in this study, such as blood pressure, blood glucose, and total cholesterol, were judged to be ideal by the questionnaire and examination, which had high credibility. In addition, the association and interaction between AR and its different types with ICVHM were studied by subgroup stratified analysis, which provides ideas for further analysis.
本次研究的优点包括：NHANES 在进行调查时采用了严格的质量保证程序，并拥有大量具有代表性的样本，可以通过加权分析推断出美国所有成年人的情况，因此能够确保数据的有效性。本研究中使用的心血管相关指标，如血压、血糖、总胆固醇等，通过问卷调查和检查判断为理想指标，可信度较高。此外，通过亚组分层分析，研究了AR及其不同类型与ICVHM之间的关联和相互作用，为进一步分析提供了思路。

Our research also had limitations. First, this study used cross-sectional data for analysis, unable to determine the causal sequence. Second, although a range of covariates was controlled for in our study, there is still a risk of unmeasured confounding and measurement errors that may have biased our results. In addition, we excluded some participants with missing data, which may have resulted in the loss of some information. However, this study still has important guiding significance for the prevention of arthritis.
我们的研究也有局限性。首先，本研究使用横截面数据进行分析，无法确定因果顺序。其次，虽然我们在研究中控制了一系列协变量，但仍有可能出现未测量的混杂因素和测量误差，从而使我们的结果产生偏差。此外，我们排除了一些数据缺失的参与者，这可能会导致一些信息的丢失。不过，这项研究对于预防关节炎仍具有重要的指导意义。

Conclusion 结论

In conclusion, higher ICVHM scores were associated with a lower prevalence of AR in U.S. adults, and similar findings were observed for OA, RA, and Other AR. These results supported the idea that AR and CVD may share common risk factors and suggested that improving cardiovascular health may prevent AR and its different types of risks. In addition, there were interactions between age, gender, and race with ICVHM on AR. Our findings guide promoting healthy behaviors and health factors, which have important implications for the prevention of AR and its different types.
总之，在美国成年人中，较高的 ICVHM 分数与较低的 AR 患病率相关，在 OA、RA 和其他 AR 中也观察到了类似的结果。这些结果支持了 AR 和心血管疾病可能具有共同风险因素的观点，并表明改善心血管健康可预防 AR 及其不同类型的风险。此外，年龄、性别和种族与有关 AR 的 ICVHM 之间存在相互作用。我们的研究结果为促进健康行为和健康因素提供了指导，这对预防 AR 及其不同类型的风险具有重要意义。

Acknowledgements 致谢

Author contributions 作者供稿

Author Contributions: Conceptualization: Yuxiang Wang, Bo Li. Data curation: Yuxiang Wang, Nan Yao. Formal analysis: Yuxiang Wang, Mengzi Sun, Shifang Qu, Fengdan Wang. Methodology: Yuxiang Wang, Mengzi Sun, Zibo Wu. Project administration: Yuxiang Wang. Visualization: Ruirui Guo, Xuhan Wang. Writing–original draft: Yuxiang Wang, Nan Yao. Writing–review & editing: Yuxiang Wang, Jing Li, Zechun Xie, Yan Liu. Bo Li is the guarantors.
作者贡献：构思：王宇翔、李博。数据整理：王宇翔、姚楠王宇翔、姚楠。形式分析王宇翔、孙梦子、曲世芳、王凤丹。方法论：王宇翔、孙梦子、吴子博。项目管理：王宇翔。可视化：郭瑞瑞、王旭涵。写作-原稿：王宇翔、姚楠。审稿与编辑：王宇翔、李静、谢艳春王宇翔、李静、谢泽春、刘艳。李波为担保人。

Funding/Support 资金/支持

This work was supported by the National Natural Science Foundation of China (No. 81973129).
这项工作得到了国家自然科学基金的支持（编号：81973129）。

Data availability 数据可用性

The dataset supporting the conclusions of this article is available in the National Health and Nutrition Examination Survey (NHANES), [hyperlink to dataset in https://www.cdc.gov/nchs/nhanes/index.htm].
支持本文结论的数据集可从美国国家健康与营养调查（NHANES）中获取，[数据集超链接见 https://www.cdc.gov/nchs/nhanes/index.htm]。

Declarations 声明

Footnotes 脚注

References 参考资料