In this study, 572 secondary school students aged 15–18 years old stage were selected to study the effect of their cognitive ability and self-discipline and planning on academic achievement. Cognitive ability was classified into memory ability, representational ability, information processing ability, logical reasoning ability, and thinking conversion ability, and analyzed the effects of these five ability values on academic achievement. The mediating effect of self-discipline ability between cognitive ability and academic achievement was analyzed using structural equation modeling (SEM), and the moderating role of planning in the mediating effect was analyzed using planning as a moderating variable. The results showed that cognitive ability can have a significant positive effect on academic achievement, while self-discipline plays a partially mediating role between cognitive ability and academic achievement, and the moderating effect of Planning is significant in the second half of the mediating effect, i.e., the effect of self-discipline on academic achievement changes as the level of planning increases, and the mediating effect is stronger in the condition of higher planning, and the mediating model with moderating effect holds. According to Both cognitive ability and self-discipline have been key factors affecting students’ academic achievement . Self-diIn this study, the cognitive ability, self-discipline, planning, and academic achievement of high school students were studied, and a structural equation with a moderating mediating effect was constructed with self-discipline as the mediating variable and planning as the moderating variable to analyze the mediating effect of self-discipline between cognitive ability and academic achievement, and the moderating effect of planning under the mediating effect.Cognitive ability refers to the human brain’s ability to store memory, process and extraction of information, includes attention, memory and logical reasoning, and thinking transformation. It is a key factor that research can consistently predict Academic Achievement . Past reAlthough there is a significant relationship between cognitive abilities and Academic Achievement, existing research is difficult to model the effect of cognitive abilities on Academic Achievement. In fact, in terms of student learning, cognitive abilities are very important in students’ learning activities, and it is not only about different cognitive abilities, but also relates to the ways in which these different abilities function together . There aThrough the research of many scholars, we can find that the effect of students’ cognitive ability on academic achievement is significant, but the complex mechanisms of their influence remain very ambiguous. The importance of cognitive abilities in students’ learning activities is only reflected in the researcher’s predetermined scope of investigation, which contains one or more cognitive abilities specific to the researcher, while outside the scope of investigation, these cognitive abilities still operate in an unpredictable manner , thus, sIn addition, Past research has tended to examine the impact of a single cognitive ability, while research under the combined influence of multiple cognitive abilities is lacking. Therefore, in this study, according to classification of cognitive abilities by Hypothesis 1: Cognitive ability can positively predict students’ academic achievement.Many studies are generally agreed by researchers that cognitively competent students have better Academic Achievement . HoweverCognitive ability and self-discipline are both independent and interrelated elements of individual students’ psychology , since cIn recent years, the correlation relationship between cognitive ability and self-discipline has received more attention, and some researchers have used long-term follow-up survey data to confirm the influence relationship between cognitive ability and self-discipline both theoretically and empirically, and found that cognitive ability can significantly influence self-discipline . Self-diHypothesis 2: Self-discipline mediates the relationship between cognitive ability and academic achievement.Planning is the psychological and behavioral characteristics of an individual’s use of time and has a multidimensional and multilevel psychological structure . PlanninAfter considering cognitive abilities and personality traits, it was found that planning does not directly affect academic achievement, but rather acts as a moderator between academic achievement. In terms of self-discipline theory, planning regulates the implementation of individual goals and tasks, and effort management, including perseverance in performing tasks and self-motivation, ensures that goals are accomplished. In addition, laxity in planning is the most obvious external manifestation of academic procrastination , which iTherefore, this study hypothesizes that self-discipline mediates between cognitive ability and academic achievement, and that planning moderates the mediating effect of self-discipline between cognitive ability and academic achievement, and proposes the following research hypothesis.Hypothesis 3: planning can positively moderate the effect of cognitive ability on self-discipline.Hypothesis 4: Planning can positively regulate the effect of self-discipline on academic achievement.Hypothesis 5: planning can moderate the mediating role of self-discipline ability between cognitive ability and academic achievement.The main research relationships of the structural equation model are shown in The ethical examination of this study was approved by the Research Ethics Committee of the School of Humanities and Social Sciences, University of Science and Technology Beijing, and the study was conducted in accordance with the regulations for the protection of human subjects. This study selected 572 students as samples, all aged 15–18 years old, As shown in Both the cognitive ability, Self-discipline and Planning measures in this research were conducted on campus. The students who took the test were organized by staff and tested in a separate classroom. The entire test lasted for 2 h.Structural equation models were developed based on the obtained students’ cognitive ability, self-discipline, planning ability, and academic achievement, and composite achievement models and sub-subject models were developed for Chinese, mathematics, and English, respectively. Each model was first tested for common method bias in the analysis process, and then the fit of the model was tested according to the CFA test procedure. When all tests were passed, the mediating effect analysis process with moderation was followed by first bringing cognitive ability, self-discipline and planning ability into the structural equation model to see the model fit, then bringing the interaction term of planning on cognitive ability and self-discipline ability into the model to compare whether the model fit was optimized, and finally testing the mediating effect of self-discipline ability with the bootstrap method and analyzing the planning with the simple slope test moderation effect.A stimulus-informed cognitive ability system designed by The test questions of information processing ability include three parts: image selection response, graphic comparison response, and image matching response. Test questions for memory ability included two parts: Number forward and reverse memory and image matching response. Test questions of expressive ability include three parts: Spatial image manipulation, spatial image reasoning, and spatial image comparison. The test question of thought conversion ability is text-image matching test. The test questions for logical reasoning ability are conceptual reasoning and logical method reasoning.The cognitive accuracy of the tested students was obtained by statistical methods, and their corresponding cognitive ability values were quantified and the quantified values were converted into T-scores to obtain the final cognitive ability values of the tested students. The final cognitive ability values contain five ability values: MA, LRA, RA, IPA, and TCA. The test method has been patented as an invention, and the sample size of the general test exceeds 2 million. The values of students’ cognitive abilities obtained from the test were normally distributed with a range of trends of ± 50 centered at 100, with high discriminant validity. The Cronbach’s alpha of the test ranged among 0.80–0.90.This study used the Self-discipline Scale designed by The planning scale was designed by In the current research, in order to reduce the influence due to the level of students’ test performance, the average of the students’ four test scores in the semester when the cognitive ability was tested to be worthy was used as the academic score for each subject, and the raw scores were standardized  = 12.092, CFI = 0.992, TLI = 0.983, SRMR = 0.018, RMESA = 0.050, 90% CI = , indicating that the fitted indicators were within the normal reception range. p < 0.001).An exploratory factor analysis was required to check the quality of the model before conducting a moderated mediated effects analysis. This study included one latent variable, namely cognitive ability, and two explicit variables, self-discipline and planning. The results of the test showed a good fit of the model with χIn this study, structural equation modeling was used to examine the effects of cognitive ability, self-discipline, and planning on academic achievement, and the results are shown in 2/df = 4.71, CFI = 0.942, TLI = 0.909, RMESA = 0.119, and SRMR = 0.065. For the mediated model with the interaction term, AIC = 73948.290, compared to the AIC value of the baseline model (74672.583), which is reduced by 724.293, indicating that the mediated model with adjustment has improved compared with the baseline model; At the same time, For the mediated model with the interaction term, Log Likelihood = –36931.145, which is 370.147 higher than the Log Likelihood of the baseline model (–37301.292), that is, the value of –2LL is 370.147, the degree of freedom of the model is increased by 8, and the chi-square test of –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Referring to the steps of analysis of mediated model with moderation summarized by p < 0.001), 95% CI = ; the interaction term of Cognitive ability and Planning was a significant predictor of Comprehensive Academic achievement , 95% CI = . It indicates that the direct relationship between Cognitive ability and Comprehensive Academic achievement is moderated by Planning.Cognitive ability was a positive predictor of Comprehensive Academic achievement , which is reduced by 8559.873, indicating an improvement of the mediated model with adjustment compared to the baseline model; meanwhile, the Log Likelihood of the mediated model with adjustment = –32943.771, compared to the Log Likelihood of the baseline model (–37230.708), increased by 4286.937, which means that the –2LL value is 4286.937. The increase in the degrees of freedom of the model is 8, and the chi-square test for the –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Second, the effect of Cognitive ability (X) on Comprehensive Academic achievement (Y) through Self-discipline (W) was tested to see if it was moderated by Planning (U), and the results are shown in p < 0.001), 95% CI = . Cognitive ability (X) can significantly predict Self-discipline (W) , 95% CI = . The interaction term (UX) of Cognitive ability (X) and Planning (U) cannot significantly predict Self-discipline (W) , 95% CI = , containing 0. Self-discipline(W) can significantly predict Comprehensive Academic achievement(Y) , 95% CI = ; the interaction term (UX) of Cognitive ability (X) and Planning (U) can significantly predict Comprehensive Academic achievement (Y) , 95% CI = ; the interaction term (UW) between Self-discipline (W) and Planning (U) can significantly predict Comprehensive Academic achievement (Y) , 95% CI = . In addition, 95% CI for a1b2, a3b1, and a3b2 were calculated using the Bootstrap method and were , , and , respectively, with only 95% CI for a1b2 not containing 0. Thus, it is evident that the Self-discipline in the mediating effect between cognitive ability and comprehensive academic achievement was significant , while the discipline was moderated by Planning in the second half of the mediating effect, the effect of Self-discipline on comprehensive academic achievement varied with the level of planning; the first half of the mediating effect of Self-discipline was not moderated by planning. Hypotheses 2 and 4 are valid, but hypothesis 3 is not.Cognitive ability (X) significantly predicts comprehensive Academic Achievement (Y) ; in the “Low Planning group,” although the predictive effect was still significant , it was weaker than in the “High Planning group.” In addition, when the process of mediation is moderated, it is required to test whether the mediating effect varies with changes in the moderating variable U, as suggested by p < 0.01), 95% CI = . This indicates that the mediation effect is stronger in the higher Planning condition and the mediation model with moderation is validated. Hypothesis 5 is valid.To further explore the moderating effect of Planning, students were divided into “high/low Planning groups” using a positive/negative one standard deviation boundary for Planning. The simple slope test see  showed t2/df = 4.63, CFI = 0.914, TLI = 0.867, RMESA = 0.118, and SRMR = 0.056. For the mediated model with the interaction term, AIC = 73863.031, compared to the AIC value of the baseline model (74568.601), which is reduced by 705.570, indicating that the mediated model with adjustment has improved compared with the baseline model; At the same time, For the mediated model with the interaction term, Log Likelihood = –36888.516, which is 360.785 higher than the Log Likelihood of the baseline model (–37249.031), that is, the value of –2LL is 360.785, the degree of freedom of the model is increased by 8, and the chi-square test of –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Referring to the steps of analysis of mediated model with moderation summarized by p < 0.001), 95% CI = ; the interaction term of Cognitive ability and Planning was a significant predictor of Chinese Academic Achievement , 95% CI = . It indicates that the direct relationship between Cognitive ability and Chinese Academic Achievement is moderated by Planning.Cognitive ability (X) significantly predicts Chinese Academic Achievement (Y), which is reduced by 8526.792, indicating an improvement of the mediated model with adjustment compared to the baseline model; meanwhile, the Log Likelihood of the mediated model with adjustment = –32907.847, compared to the Log Likelihood of the baseline model (–37178.242), increased by 4270.395, which means that the –2LL value is 4270.395, The increase in the degrees of freedom of the model is 8, and the chi-square test for the –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Second, the effect of Cognitive ability (X) on Chinese Academic achievement (Y) through Self-discipline (W) was tested to see if it was moderated by Planning (U), and the results are shown in p < 0.001), 95% CI = . Cognitive ability (X) can significantly predict Self-discipline (W) , 95% CI = . the interaction term (UX) of Cognitive ability (X) and Planning (U) cannot significantly predict Self-discipline (W) , 95% CI = , containing 0. Self-discipline(W) can significantly predict Chinese Academic Achievement(Y) , 95% CI = ; the interaction term (UX) between Cognitive ability (X) and Planning (U) cannot significantly predict Chinese Academic Achievement (Y) , 95% CI = , containing 0; the interaction term (UW) between Self-discipline (W) and Planning (U) cannot significantly predict Chinese Academic Achievement (Y), 95% CI = , containing 0. In addition, 95% CI for a1b2, a3b1, and a3b2 were calculated using the Bootstrap method and were , , and , respectively, with 95% CI all contained 0. Therefore, the mediating effect of Self-discipline between Cognitive ability and Chinese Academic achievement was significant , but the moderating effect of Planning was not significant.The predictive effect of Cognitive ability (X) on Chinese Academic Achievement (Y) was significant , which is reduced by 700.901, indicating that the mediated model with adjustment has improved compared with the baseline model; At the same time, For the mediated model with the interaction term, Log Likelihood = –36990.486, which is 358.480 higher than the Log Likelihood of the baseline model (–37348.966), that is, the value of –2LL is 358.480, the degree of freedom of the model is increased by 8, and the chi-square test of –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Referring to the steps of analysis of mediated model with moderation summarized by p < 0.001), 95% CI = ; the interaction term of Cognitive ability and Planning was a non-significant predictor of Mathematics Academic achievement was not significantly predicted by the interaction term between Cognitive ability and Planning , 95% CI = , containing 0. This indicates that the direct relationship between Cognitive ability and Mathematics Academic achievement was not affected by Planning of the direct relationship was not moderated by Planning.Cognitive ability was a positive predictor of Mathematics Academic achievement , which is reduced by 8527.070, indicating an improvement of the mediated model with adjustment compared to the baseline model; meanwhile, the Log Likelihood of the mediated model with adjustment = –33007.595, compared to the Log Likelihood of the baseline model (–37278.130), increased by 4270.535, which means that the –2LL value is 4270.535, The increase in the degrees of freedom of the model is 8, and the chi-square test for the –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Self-discipline (W) was tested to see if it was moderated by Planning (U), and the results are shown in p < 0.05), 95% CI = . Cognitive ability (X) can significantly predict Self- discipline (W) , 95% CI = . The interaction term (UX) of Cognitive ability (X) and Planning (U) cannot significantly predict Self-discipline (W) , 95% CI = , containing 0. Self-discipline(W) can significantly predict Mathematics Academic achievement(Y) , 95% CI = ; the interaction term (UX) between Cognitive ability (X) and Planning (U) cannot significantly predict Mathematics Academic achievement (Y) , 95% CI = ; the interaction term (UW) of Self-discipline (W) and Planning (U) can significantly predict Mathematics Academic achievement (Y) , 95% CI = . In addition, 95% CI for a1b2, a3b1, and a3b2 were calculated using the Bootstrap method and were , , and , respectively, with only 95% CI for a1b2 not containing 0. Thus, It is clear that the mediating effect of self-discipline between cognitive ability and academic achievement in mathematics was significant , while the discipline’s mediating effect was moderated by planning in the second half, the effect of Self-discipline on Mathematics Academic achievement varied with the level of Planning; the first half of Self-discipline’s mediating effect was not The first half of the mediating effect of Self-discipline was not moderated by Planning.Cognitive ability (X) significantly predicts mathematics Academic Achievement (Y) ; in the “Low Planning group,” although the predictive effect was still significant , it was weaker than in the “High Planning group.”To further explore the moderating effect of Planning, students were divided into “high/low Planning groups” using a positive/negative one standard deviation boundary for Planning. The simple slope test see  showed tp < 0.05), 95% CI = . This indicates that the mediation effect is stronger in the higher Planning condition and the mediation model with moderation is validated.In addition, when the process of mediation is moderated, it is required to test whether the mediating effect varies with changes in the moderating variable U, as suggested by 2/df = 4.64, CFI = 0.911, TLI = 0.861, RMESA = 0.118, and SRMR = 0.058. For the mediated model with the interaction term, AIC = 74024.164, compared to the AIC value of the baseline model (74728.602), which is reduced by 704.438, indicating that the mediated model with adjustment has improved compared with the baseline model; At the same time, For the mediated model with the interaction term, Log Likelihood = –36969.082, which is 360.219 higher than the Log Likelihood of the baseline model (–37329.301), that is, the value of –2LL is 360.219, the degree of freedom of the model is increased by 8, and the chi-square test of –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Referring to the steps of analysis of mediated model with moderation summarized by p < 0.001), 95% CI = ; the interaction term of Cognitive ability and Planning was a non-significant predictor of English Academic achievement , 95% CI = , contains 0. This indicates that the direct relationship between Cognitive ability and English Academic achievement is not moderated by Planning of moderation.Cognitive ability was a positive predictor of English Academic achievement , which is reduced by 8526.839, indicating an improvement of the mediated model with adjustment compared to the baseline model; meanwhile, the Log Likelihood of the mediated model with adjustment = –32987.897, compared to the Log Likelihood of the baseline model (–37258.317), increased by 4270.420, which means that the –2LL value is 4270.420, The increase in the degrees of freedom of the model is 8, and the chi-square test for the –2LL value is significant (p < 0.05), so the mediated model with adjustment fits better than the baseline model.Second, the effect of Cognitive ability (X) on English Academic achievement (Y) through Self-discipline (W) was tested to see if it was moderated by Planning (U), and the results are shown in p < 0.05), 95% CI = . Cognitive ability (X) can significantly predict Self-discipline (W) , 95% CI = . The interaction term (UX) of Cognitive ability (X) and Planning (U) cannot significantly predict Self-discipline (W) , 95% CI = , containing 0. Self-discipline(W) can significantly predict English Academic achievement(Y) , 95%CI = ; the interaction term (UX) between Cognitive ability (X) and Planning (U) cannot significantly predict English Academic achievement (Y) , 95% CI = ; the interaction term (UW) between Self-discipline (W) and Planning (U) cannot significantly predict English Academic achievement (Y) , 95% CI = . In addition, 95% CI for a1b2, a3b1, and a3b2 were calculated using the Bootstrap method and were , , and , respectively, 95% CI containing 0. Thus, it can be seen that Self-discipline in Cognitive ability and English Academic achievement was significant , but the moderating effect of Planning was not significant.Cognitive ability (X) significantly predicts English Academic Achievement (Y)  mainly refers to students’ ability to comprehend information after obtaining it through reading and listening, and is closely related to students’ classroom efficiency. Students with higher IPA ability can fully understand and master what teachers teach in class and quickly construct their own knowledge system, thus improving their knowledge mastery and achieving better academic achievement in exams . The effTCA (Thinking Conversion Ability) refers to the student’s active thinking in the learning process to understand knowledge, mainly in the speed and accuracy of thinking conversion, therefore, this ability can facilitate learning in various disciplines, especially in mathematics, where students with high TCA ability can more easily summarize existing knowledge and expand new thinking and skills in the problem solving process, and to make analogies in similar problems, thus improving the accuracy of solving novel and difficult problems, and thus improving their academic achievement .MA (memory ability) mainly refers to students’ long term memory ability. the stronger the MA ability value, the more students can remember knowledge quickly and retain it over time . In addiLRA  includes both inductive and deductive reasoning types. Recently, higher education entrance examinations in China have begun to focus on students’ reasoning ability, which is also reflected in the addition of a large number of logical reasoning questions in Chinese and English subjects ; therefoRA  is a key cognitive ability that can effectively help students understand mathematical spatial imagery-like knowledge content . Also, RThe present study showed that self-discipline partially mediates the relationship between cognitive ability and Academic Achievement. Self-discipline is a behavioral habit, and self-management is the essence of self-discipline. Self-discipline follows certain principles and norms and relies on the student’s own willpower to accomplish the desired goal’s behavioral ability without supervision .A higher level of self-discipline means that students are more able to concentrate and resist external temptations during the learning process, which can help them be more effective in their studies. Especially for high school students, the higher the value of self-discipline, the better they can make the most of their time, the more efficient and independent thinking they can do, thus improving their understanding and mastery of knowledge and leading to improved academic achievement. In addition, according to the teaching schedule in Beijing, school ends at 16:30 every afternoon and students manage the rest of the day by themselves. Students with high self-discipline can fully and rationally use their time, thus consolidating what they have learned, improving their understanding and mastery, and achieving better overall academic results in academic exams.The stronger the cognitive ability of students, the more efficient students are in their studies, the more focused they are in their studies, and the more likely they are to achieve a sense of academic achievement . TherefoSpecifically, self-discipline plays a partially mediating role in overall academic achievement, with a mediating role of 0.263 and a mediating effect of 38.3%; in Chinese academic achievement, self-discipline plays a partially mediating role, with a mediating role of 0.105 and a mediating effect of 27.1%; in mathematics academic achievement, self-discipline plays a partially mediating role, with a mediating role of 0.157 and a mediating effect of The mediating effect of self-discipline in English academic achievement was partially mediated by 0.134, with a mediating effect of 49.8%. As can be seen, the mediating effect of self-discipline is more pronounced in mathematics and English subjects, which is because the examinations of mathematics subjects pay more attention to the assessment of students’ thinking ability, which requires students to think and train for a long time, especially in TCA and LRA, which require students to improve and show these abilities in a long time and highly focused learning process, so for students with strong cognitive ability, the therefore, for students with strong cognitive abilities, the stronger their self-discipline and the longer they focus during the examinations, the more they can show the characteristics of their TCA and LRA abilities, and the more they can achieve better academic results during the examinations. In addition, in the English subject test subjects, the effect of the mediating role of self-discipline in multiple English subjects also appears to be prominent as the test questions become increasingly important in assessing students’ thinking over and above the assessment of mastery of basic knowledge  with theThe present study found that planning moderates the second half of academic achievement by influencing academic achievement. Specifically, students with high plannings were more likely to affect academic achievement through cognitive ability compared to students with low plannings, and hypotheses 4 and 5 were tested. Furthermore, in contrast to our expectations, planning did not moderate the direct effect of cognitive ability and the first half of the mediating effect.The moderating effect of planning was significant in the second half of the mediating effect. planning is an important component of an individual’s self-regulated learning strategy, and as a personality trait, it can stimulate factors such as an individual’s motivation to learn and the ability to self-regulate learning activities, thus facilitating the accomplishment of learning goals , and stuIn the first half of the mediating effect, the moderating effect of planning is not significant. The reason for this is that in the stage of influence of cognitive ability on self-discipline, it is mainly through the sense of academic achievement and academic self-confidence built up by cognitive ability that positively influences self-discipline and thus obtains better positive feedback, and this sense of academic achievement does not change with the adjustment of academic plan, so planning is not significant in regulating the influence of cognitive ability on self-discipline.Also, among the subject-specific subjects, the moderating effect of planning was significant among academic achievement in mathematics, but not in Chinese and English. This is because for mathematics subjects, learning requires more rigorous logical arrangement and reasonable time security in order to fully understand and digest the knowledge learned and to improve one’s thinking ability, so as to improve academic achievement in mathematics. In contrast, Chinese and English subjects are more important to the accumulation of daily knowledge, which requires students to persist for a long time to see the effect, which is not related to the planning of learning arrangements , so the In addition, the simple slope test revealed that when self-discipline is low, students with low planning ability perform better than students with high planning ability; when self-regulation is high, students with high planning ability perform better than students with low planning ability. This is due to the fact students with weak self-discipline, the stronger their planning ability and the more reasonable their time planning, the more likely they are to put pressure on themselves, which leads to weak execution ability and the inability to complete the planned study tasks, thus leading to lower and lower academic achievement. In contrast, when self-discipline is high, the stronger the planning ability and the more reasonable the time planning arranged, the more it helps students to improve their learning efficiency and give full play to their cognitive ability, thus excelling in academic achievement.In this study, only the external influences caused by two of the personality traits, self-discipline and planning, were considered in the analysis of the influence of cognitive ability on sustained academic achievement; similarly, the influence of other psychological states of the students on cognitive ability and academic achievement was not considered in the analysis. In addition, one of the most prominent limitations of this study is the small sample size and the single range of students investigated. To further enhance the credibility of the study results, more schools in other Chinese provinces should be selected for study and comparison. Future research could focus on this area to obtain more valuable findings.This study used structural equation modeling to analyze the moderating effect of panning on the mediating effect of self-discipline on the relationship between cognitive ability and academic achievement. The results showed that cognitive ability can have a significant positive effect on academic achievement, while self-discipline plays a partially mediating role between cognitive ability and academic achievement, and the moderating effect of Planning is significant in the second half of the mediating effect, i.e., the effect of self-discipline on academic achievement changes as the level of planning increases, and the mediating effect is stronger in the condition of higher planning, and the mediating model with moderating effect holds.The original contributions presented in this study are included in the article/The studies involving human participants were reviewed and approved by the Research Ethics Committee of the School of Humanities and Social Sciences, University of Science and Technology Beijing. Written informed consent to participate in this study was provided by the participants or their legal guardian/next of kin.YS contributed to the conception and design of the study and performed the statistical analysis. YS and SQ contributed to the data collection and wrote the first draft of the manuscript. Both authors contributed to the manuscript revision, read, and approved the submitted version.


Cystic fibrosis (CF), which is the most common inherited genetically determined disease caused by a mutation in the gene for the CF transmembrane conductance regulator protein. Pulmonary failure is the leading cause of death in this population, while the dysregulation of endocrine system creates significant disorders, including malnutrition, underweight, and CF-related diabetes. Therefore, the objective of our study was to determine the following hormones in the serum of patients with CF: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). To our knowledge, serum levels of PYY, ASP, and α-MSH have not yet been assessed in CF. For this purpose, we measured hormone levels using enzyme-linked immunosorbent assays in 38 patients from the local CF care center, as well as 16 sex- and age-matched healthy controls. Moreover, we estimated the correlations between the tested hormones and the parameters of the patients’ clinical status. In this study, we found sinificantly reduced serum levels of ghrelin and ASP in patients with CF (p<0.01). There was no difference in PYY and α-MSH levels between participants with CF and healthy subjects. Furthermore, there was no difference in hormone levels between females and males with CF. The type of gene mutation (homozygous or heterozygous for ΔF508) had no effect on hormone levels. Ghrelin was negatively correlated with age, body mass index, and C-reactive protein. PYY was negatively associated with the age of the patients. Hormone dysregulation in CF may contribute to decreased appetite, as well as many other disturbed processes. Therefore, ghrelin appears to play a key role in the regulation of energy management of CF. Future multicenter and multidisciplinary studies should focus on an unequivocal understanding of the role of these hormones in CF. Cystic fibrosis (CF) is a multisystem disease caused by mutations in a single gene located on human chromosome 7 that encodes the cystic fibrosis transmembrane conductance regulator (CFTR) protein − an epithelial chloride channel with wide tissue expression. CF affects many organs, including the lungs, exocrine and endocrine pancreas, liver and intestines, bone, sweat gland, and male reproductive tract . NeverthTherefore, the objective of our study was to determine the following hormones in the serum of CF patients: ghrelin, putative peptide YY (PYY), Agouti-signaling protein (ASP), and alpha-melanocyte-stimulating hormone (α-MSH). Ghrelin is a multifaceted gut hormone and plays a crucial role in the release of growth hormones, food intake, fat deposition, glucose and energy homeostasis, cardioprotection, muscle atrophy, and bone metabolism . PYY is The Rzeszów University Bioethics Committee approved the study protocol (2022/023). All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the Declaration of Helsinki of 1964 and its subsequent amendments or comparable ethical standards. The informed consent of the patient and/or legal guardian was obtained in writing.A cross-sectional study of a single center was carried out on thirty-eight patients with CF and sixteen control patients. Participants were recruited from the CF clinic of the Department of Allergology and Cystic Fibrosis, Provincial Hospital No. 2 in Rzeszow from February to October 2021.1) greater than 35% of predicted stable pulmonary disease as defined by both clinical impressions and no hospitalizations within 1 month of screening. The exclusion criteria were as follows: heart failure and liver insufficiency, psychiatric disorders, lung transplantation, cystic fibrosis-related diabetes, obesity, corticosteroids treatment, gastrostomy tube feeds or parenteral nutrition and appetite stimulants. Furthermore, if the patients were unable to perform spirometry and refused to participate in the study, they were excluded. All patients with CF suffered from pancreatic insufficiency and received regularly pancreatic enzyme replacement therapy . Patients were also treated with human DNase I recombinant , fat-soluble vitamins in the form of ADEK tablets , nutrition drinks  and inhalation of 3–10% sodium chloride 3–4 times daily. All patients were clinically evaluated, showing no signs or symptoms of malabsorption, and had a stable weight for at least 2 months prior to the study. Information on the type of CFTR mutation (homozygous or heterozygous for ΔF508) as well as other clinical parameters was obtained from hospital patient records. Additionally, information on bacterial infections with Pseudomonas aeruginosa and/or Staphylococcus aureus in the sputum was obtained from hospital patient records.The study included Caucasian patients with CF and a confirmed diagnosis based on determination of sweat chloride, genetics, and immune-reactive trypsin tests in neonatal age (patients born in or after 2009). Patients met all of the following inclusion criteria to be eligible for participation in this study: forced expiratory volume in the first second  according to recommendations . We calcBlood samples were collected between 8 am and 10 am after a night of fasting and placed in blood collection tubes. The collected serum was incubated at room temperature for at least 30 min, and centrifuged . Subsequently, the serum was transferred to cryovials and placed immediately in the freezer at −80°C until further analysis. The serum sample was thawed only once on the day of analysis.Blood morphology was performed using a hematology analyzer . C-reactive protein (CRP) concentration was estimated using the dry chemistry immunological method on a VITROS 250 analyzer .Serum hormone concentrations after an overnight fast were measured in duplicates with a previous dilution using commercially available enzyme-linked immunosorbent assays , according to the manufacturer’s protocol.All statistical analyses were performed with the STATISTICA software package . Data are expressed as mean and SD, as well as range. The normality of the distribution was validated using the Shapiro-Wilk test, as well as skewness values. The Mann-Whitney U test was used to compare differences between two independent groups. The correlation analysis was performed using the Spearman correlation test, assuming linear dependence with α=0.05.In our study, seventeen females and eleven males with CF were included in the CF group, as well as healthy ten females and six males were recruited into the control group. Basic characteristics, clinical laboratory values, and lung function indices for patients with CF and healthy participants are shown in P. aeruginosa, 11 were infected with S. aureus, 9 were co-infected with P. aeruginosa and S. aureus, while 9 were uninfected.The mean age in the CF patient group was 19.58 ± 7.9 years, while the healthy subjects were 19.25 ± 7.3 years old. There were no differences in the age and height of the study groups. CF patients had statistically lower body weight than healthy controls. The BMI was similar in adult patients with CF and healthy volunteers. 30 participants with CF were homozygous for ΔF508 and 8 (21.1%) were heterozygous. CF patients had significantly higher white blood cell counts and CRP levels. Lung function was decreased in the CF group compared to healthy subjects. Based on the spirometry results, more than 60% of the patients had mild disease, 23.7% of the patients had moderate and 15.8% of the patients had severe disease. Among patients with CF, 9 were infected with The levels of hormones studied are presented in Moreover, there was no association between the type of CFTR mutation and the level of the tested hormones Table 3.The next step was to try to determine the correlation between the levels of the hormones studied and the clinical parameters of CF patients. Associations between hormones and clinical data are presented in Ghrelin was negatively correlated with age, BMI in patients older than 20 years, and CRP. Furthermore, we found a strong negative correlation between ghrelin and leptin concentration in the sera of patients with CF . Ghrelin was also positively correlated with the level of KISS  and POMC . PYY was negatively associated with the age of the patients  as well as with serum leptin levels . α-MSH negatively correlated with the level of neuropeptide Y. ASP levels were not correlated with any of the parameters tested and their concentration was not correlated with other hormones studied. It should be noted that none of the hormones studied was correlated with the results of spirometry.Our study presents for the first time circulating levels of the hormones that regulate energy metabolism and nutrition, such as the putative peptide YY, the Agouti-signaling protein and the alpha-melanocyte-stimulating hormone in patients with CF. The main findings of our study are a significantly decreased level of ghrelin and ASP in the sera of patients with CF compared to healthy controls. Furthermore, we found that PYY and α-MSH did not differ in CF patients and healthy participants.Eating and satiation feelings involve complex interactions between many hormones from the gastrointestinal tract to the hypothalamus and subsequent feedback . ChronicWe found a decreased level of ghrelin in CF participants. Contrary to our results, the levels of ghrelin in the serum of children with CF patients were significantly higher than those of the control group . On the We have also found significantly lowered level of ASP in CF participants. Human ASP is expressed at the highest levels in adipose tissue where it is a competitive antagonist of the α-MSH to bind to receptor . So far,Peripheral PYY has been reported to act as a satiety signal, regulating the termination of individual meals, in part by reducing the production of the hunger-stimulating peptide ghrelin. In our study, we did not find differences in PYY levels between patients with CF and healthy controls. Higher total plasma PYY levels were reported in patients with anorexia nervosa compared to lean, obese, or morbidly obese subjects . HoweverThe α-MSH, an endogenous neuropeptide derived from POMC, is widely expressed in various tissues and organs and plays an important role in a variety of biological processes, such as energy metabolism, body weight regulation, sexual activity, and exocrine secretion . This ho1 and ghrelin  had been reported in the study by Cohen et al.  in obese men . Written informed consent to participate in this study was provided by the participants’ legal guardian/next of kin.Conceptualization, SG and AM. Data curation, SG and RP. Formal analysis, SG. Investigation, SG and RP. Methodology, SG and RP. Project administration, SG. Resources, SG and MR. Software, SG. Supervision, SG. Writing−original draft, SG. Writing−review and editing, SG, RP, MR and AM. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Results: Dependency relationships were found between self-perceived health and PA levels, in both genders and in different relationships with smoking (x2 < 0.001). Inactivity was related to higher prevalences of negative health perception (p < 0.05) in all groups analyzed. Inactive smokers (OR: 6.02. 95% CI: 3.99–9.07. RR: 5.24. 95% CI: 3.56–7.73) presented increased risks of negative health perception compared to people with low/medium PA levels, similarly found in other relationships with tobacco. Conclusions: Increasing the PA level of the smoking population could reduce the negative effects on their perceived health. Medium and high PA levels reduce the risk of negative health perception in the Spanish population, both in smokers, ex-smokers, and non-smokers.Background: Smoking is associated with poor health status. Increased prevalence of multiple diseases has been found in populations of smokers and ex-smokers. Physical activity (PA) could reduce the negative effects of smoking. Aims: To analyze the relationships between smoking and self-perceived health and between PA level and self-perceived health, according to the relationship with smoking in the Spanish population. To calculate the risks of perceiving negative health in relation to smoking, according to the PA level of the population. Hypothesis: A higher level of PA reduces the risk of perceiving negative health in the Spanish smoking population. Design and Methodology: Cross-sectional study with data from 17,708 participants, 15–69 years old, interviewed in the Spanish National Health Survey 2017. Intergroup differences were studied. Odds ratios (OR) and relative risks (RR) and their confidence intervals (95% CI) were calculated for negative self-perceived health. A Spearman’s  In Spain, there has been a reduction in the proportion of smokers in recent decades, with the prevalence of tobacco use in the Spanish population falling from a third to a quarter of the population from the early 1990s to the present , being tSmoking has been associated with a large number of pathological conditions. It is associated with an increased risk of coronary artery disease, increased risk of atherosclerosis, associated with 17 types of cancers, mental illness, pulmonary fibrosis, and chronic obstructive pulmonary disease ,6, amongThe SPH, regardless of the relationship with smoking, is a factor to be taken into account in the population, being widely used, given its reliability and reliability to assess the health of people in a quick and simple way, obtaining relevant information on the health status of the population through interviews or questionnaires . The mosThe field of knowledge demonstrating the multiple health benefits of physical activity (PA) is very broad in the scientific literature , consideSome studies have even found that PA could mitigate the negative effects of smoking . In contFor this reason, the objectives of this research were: to analyze the relationships between SPH and the relationship with smoking in the Spanish population; to analyze the relationships between the level of PA and the relationship with smoking in the population, as well as the relationships between the level of PA and SPH health, according to the relationship with smoking in the Spanish population, in the general population, and by sex. In addition to calculating the risks of having a negative SPH in relation to smoking, according to the PA level of the population. It was hypothesized that: performing PA reduces the prevalence of negative SPH in the Spanish smoking population and that physical inactivity increases the risks of presenting a negative HPS in the smoking population compared to performing moderate and/or intense PA.Approval by an accredited Ethics Committee was not required. The data used for this research were obtained from non-confidential public files of the Spanish National Health Survey 2017, provided by the Ministry of Health, Consumption and Social Welfare (MSCBS), according to Regulation (EU) 2016/679 of the European Parliament and Council of 27 April 2016 on the protection of individuals with regard to the processing of personal data and the free movement of such data.The design of this research consisted of a descriptive cross-sectional study, based on the data obtained in the ENSE 2017, adult questionnaire , by inteThis research had a final sample of 17,708 participants between 15 and 69 years of age: 8482 men and 9226 women. To arrive at this sample, data were taken from the 23,089 people surveyed in the ENSE 2017, excluding those over 70 years of age, as they were not questioned about the PA performed, as well as 60 participants, for not including data in the PA questions, and 9 participants, for not including data on their relationship with tobacco.To form the initial sample of the ENSE 2017, the selection of participants was carried out using a stratified three-phase random sampling system, considering the Spanish population aged 15–103 years.From the ENSE 2017 , data weDerived from the data collected on these variables, the following variables were created:Age groups: youth (18–34 years. 1), young adults (35–49 years. 2), older adults (50–64 years. 3), and seniors (65–69 years. 4) [Gender group: men (1) and women (2).SPH groups: based on responses to item G.21 , groups were created: (1) Negative (grouping participants with “Bad” or “Very bad” responses. (2) Fair (grouping participants with “Fair” responses), and (3) Positive , “Yes, but not daily” (2), “I do not currently smoke, but I have smoked before” (3), “I do not smoke, nor have I smoked regularly” (4), “Don’t know”, and “No answer” (NS/NC). Groups were created: Smokers (1), Occasional smokers (2), Ex-smokers (3), Smokers (2), and Non-smokers (4), depending on the answer given to the question.Physical activity index (PAI): Index created to quantify the physical activity carried out by the population, taking the participants’ responses to the items: Q.113, Q.114, Q.115, and Q.116; questions from the International Physical Activity Questionnaire (IPAQ) in its Spanish version [ version  included version . The for version .The PAI could take values between 0 and 67.5, then the population was ordered from highest to lowest PAI, and the population’s PAI percentiles were calculated to create the different physical activity levels (PAL).Physical activity level (PAL). Four PA level groups (PAL) were formed according to the values achieved in the PAI. Participants were grouped into the following PA levels: inactive  of the ENSE 2017, “No day more than 10 min in a row”), walker , active , very active .The statistical software IBM SPSS Statistics version 25  was used to perform all statistical procedures.rho, to carry out a correlation analysis between variables. For all this, a significance level < 0.05 was established.First, the distribution followed by the variables of interest was tested using the Kolgomorov–Smirnov test. Subsequently, the sample was characterized by means of descriptive analysis, presenting the data with the central values of the population: median and interquartile range (continuous variables) and in absolute and relative frequencies , performing non-parametric tests to verify the existence of possible inter-group differences between sexes: Mann Whitney U (continuous variables) and z-test for independent proportions . The chi-square statistic was used to analyze possible dependence relationships between the ordinal variable: SPH with respect to PAL and with the relationship with smoking of the participants in the general population and in the different subgroups. Finally, odds ratios (OR) and relative risks (RR) were calculated, with their respective confidence intervals (95%CI), in addition to Spearman’s Insufficient evidence was found to be able to assume the normality followed by the distributions of the variables of interest after performing the Kolgomorov–Smirnov test.p = 0.313 in the Mann–Whitney U-test) (p = 0.286 in the chi-square test)  . Similarre test) .p < 0.001 in the chi-square test), with a higher number of male smokers than female smokers , more men than women who had quit smoking tobacco  and a higher number of women than men who had never smoked  ( z-test) .p < 0.001, chi-square test) , and men performing more high/very high level PA than women  Regarding PAL and sex, significant differences were found (re test) , with wop < 0.001, chi-square test). Significant differences were found between the proportions of people with positive SPH (good or very good), according to the relationship they had with smoking   .p < 0.05, z-test). However, they were higher in men (4.5 percentage points) than in women (1.9 points); the prevalence of men and women with negative SPH in ex-smokers showed a difference of 0.3 percentage points, whereas these differences reached 2.9 percentage points between sexes in non-smokers with negative health. Regular SPH status also showed differences in proportions between the different tobacco-related conditions, from 21.7% in Ex-smokers to 17% and 18% in Occasional and Non-smokers. However, these differences were only found in men, being even larger: 8.2 percentage points between Ex-smokers and Non-smokers, being statistically significant differences . In women, no differences were found in the proportions of Regular HPS in the four groups of smoking relationships, with a prevalence of 21–22% in all cases  of the general population. In all cases, the proportions of people with a positive SPH were higher in the higher PALs than in the Inactive and Walkers, showing significant differences  . These differences were as high as 29.5 percentage points in Non-smokers, with similar differences found in all other smoking-related conditions; however, in Ex-smokers and Non-smokers, significant differences were found between the proportions of the four PA groups . Conversely, the proportions of people with negative SPH were found to be higher in the Inactive than in the higher PALs for all tobacco-related conditions, and these differences were significant . In Inactive smokers had a proportion of 15.4% compared to 2.9% in Active smokers, a 12.5 points difference . These differences were as high as 18.7 percentage points between Very Active and Inactive ex-smokers . SPH Regular also saw reduced proportions of Inactives and Actives in all smoking relationships except Smokers. In contrast, this was true for all smoking relationships between Inactives and Very actives  ( z-test) . In the  z-test) .The odds of having a negative SPH in the Inactive groups were found to be increased in Smokers, Ex-smokers, and Non-smokers relative to the higher PAL groups, from Walkers to Very active .In Smokers, significant ORs and RRs were found between Inactives and the rest of PAL, from Walkers (OR: 2.27. 95%CI: 1.78–2.91. RR: 2.08. 95%CI: 1.67–2.58), the group with the lowest increased risk, versus Actives (OR: 6.02. 95%CI: 3.99–9.07. RR: 5.24. 95%CI: 3.56–7.73), the group with the highest increased risk. These risks were even higher in Ex-smokers  and Non-smokers . In addition, weak to moderate correlations were found across the different smoking relationship conditions between PAL and negative health perception or not .rho, presented weak and moderate correlations, although statistically significant (p < 0.001) between sex (rho = −0.068), age group , PAL , and smoking relationship .Finally, the correlation analysis found that SPH, through Spearman’s Among the main findings, it was found that among respondents aged 18–69 years living in Spain, 46.1% reported never having smoked, and 53.9% reported having had some kind of relationship with tobacco, with current smokers accounting for 25.9%. This percentage is slightly higher than the 22.3% shown by the WHO in 2020 for the world population that habitually used tobacco, where the percentage of male smokers (36.7%) was clearly higher than that of women (7.8%), a difference that was also shown in our research . DependeIn the present research, we found dependence relationships between PAL and the sex of the participants, with a higher proportion of female walkers than male walkers and a higher proportion of males performing high or very high PAL compared to females, these differences being statistically significant. These results are in line with other studies; for example, Moral-García et al., in a sample of 516 adolescents aged 12 to 16 years, showed that females perform more moderate intensity PA than males, with the male gender being more active and carrying out moderate to vigorous intensity PA . This coDependence relationships were found between SPH and smoking status. In the general population, statistically significant differences in proportions were established in men and women, with a higher proportion of occasional smokers and non-smokers than smokers and ex-smokers for SPH positive in the general population and in men . In the case of negative SPH, a higher proportion of smokers and ex-smokers than occasional smokers or non-smokers were found in the general population and in men , and these differences were statistically significant.In the study by AlDukhail et al., a higher negative SPH was also observed in US smokers and ex-smokers aged 18–65 years and older than in people who never smoked, and these percentages were higher than in the present study. This may be due to the fact that the data were collected during the COVID-19 pandemic and also that regular SPH was not taken into account, with people who answered “regular” in their self-assessment of their health being considered SPH negative. However, in their study, the proportions of negative SPH were slightly higher in smokers (21%) than in ex-smokers (19.3%), contrary to our research (7.4% smokers and 8.1% ex-smokers) . The samFemales had higher prevalences of negative SPH than males in all four categories of smoking relatedness. This is similar to what happened in other studies, for example, in the case of adolescents aged 14–19 years, where the prevalence of negative SPH was 33% in females compared to 19% in males. The percentages in the study by Silva et al. were higher than in the present study because, in their research, the SPH alternatives were established dichotomously (positive and negative), introducing the “regular” response in the negative SPH, with the percentages of positive SPH being similar to those in the present study . As theoIn line with the initial hypothesis, dependent relationships were found between PAL and SPH in the general population according to smoking status. As in other studies, better SPH was associated with higher PAL . In the Finally, our study performed a calculation of the risk of having a negative SPH when the population is smokers. This calculation showed that inactive smokers had a higher risk of having a negative SPH than walkers . Moreover, the higher the PAL (active and very active), the lower the risk of having a negative SPH  and . However, active subjects were observed to have a similar risk to very active subjects . Comparing these negative SPH ORs with ex-smokers and non-smokers, we observe that the results are similar to those of smokers, i.e., being more inactive might increase the risk of having a negative SPH than more active subjects.These results are in line with those obtained by Piko et al. in their study of adolescents. People who self-perceived their fitness as poor/regular were associated with a higher likelihood of negative/regular SPH  than people who self-perceived it as good/excellent. For smoking status, regular smokers were associated with a higher likelihood of negative/regular SPH  than non-smokers . In the In relation to the data reflected in our research, apart from the PAL showing the influence on people’s SPH, smoking status also has some impact on a person’s SPH. In several studies, it was shown that being a smoker or ex-smoker influenced a person’s SPH, with smokers and ex-smokers being more likely to have a negative SPH than people who never smoked in both men and women ,59.Although smoking is associated with poorer SPH, physical inactivity may be an even more important factor, outweighing the negative effects of smoking on population SPH, whereas PA could mitigate these effects. Therefore, moderate and/or intense PA should be recommended for smokers, non-smokers, and ex-smokers alike, if the aim is to improve the population’s SPH. Therefore, both public administrations and health services at the national and regional levels could plan strategic actions to favor a reduction in the prevalence of negative SPH through the promotion of active lifestyles by means of regular PA practice.In promoting an increase in PAL to reduce the OR of a negative SPH, it would be advisable to invest in health education and training throughout the life cycle. In this sense, it would be interesting to promote multidisciplinary work where professionals from different fields would work in a coordinated manner to achieve this proposal, with sports science professionals being key to prescribing physical exercise adapted to the patient’s conditions.In relation to the above, lack of time or desire is one of the main reasons for not engaging in PA and the adoption of sedentary behavior ,61, and In the present research, we encountered some limitations; for example, we did not carry out a gender differentiation in the study of the association of PA level with the risk of negative SPH. Therefore, as a future line of research, it would be innovative to explore how PA level influences each sex when differences in SPH between men and women are detected.One of the main limitations of the study was the measurement of SPH from a single question, as Cullati et al. state in their study, the differences in the percentages of the overall variance explained by the way SPH was assessed were not equivalent in their ability to capture the overall health of respondents . MoreoveCause–effect relationships could not be established as this was a cross-sectional study based on national health surveys, which is an intrinsic limitation of the study design. Therefore, future research could complement the findings of this study with research designs that can establish causal relationships. For example, carrying out this work longitudinally with objective PA data through public institutions such as the Ministry of Health itself would improve and contrast the results obtained in this survey. The research deals with self-reported PA data, and since it is not objective data, subjects may overestimate or underestimate when measured subjectively. Therefore, future research could use methods and materials conducive to measuring PA objectively.The type of PA performed by each individual was not taken into account, which may have some influence on the individual’s SPH.Certain variables were not introduced, such as economic status and level of education, among other socio-demographic, socio-cultural, and socio-economic biases, which could exert some influence on people’s HPS, as has been shown in other studies ,70,71. IThe present study did not take into account whether the participants had comorbidities associated with smoking, i.e., whether they suffered from cardiorespiratory pathologies such as lung cancer, Chronic Obstructive Pulmonary Disease (COPD), etc. These diseases could exert some influence on the individual’s SPH and even on his or her PAL. Therefore, another future line of novel research would be to study the prevalence of SPH and its association with PAL in various pathologies, especially those related to smoking status, such as COPD or other cardiorespiratory diseases.The population groups of current and former smokers in Spain had worse SPH than non-smokers. Habitual or former smoking was associated with a higher prevalence of people with negative SPH in Spain, both in the general population and in both sexes.The relationship with tobacco in the population showed a relationship of dependence on the PAL. There is a higher prevalence of smokers and ex-smokers in the inactive population groups or those who only walk, compared to those with a higher PAL, including moderate and/or intense activities, which is found both in the general population and in both sexes.SPH was related to PAL in all population groups, depending on their relationship to smoking. Belonging to the Inactive group was related to a higher prevalence of negative SPH versus Walking or moderate and/or intense PA in smokers, ex-smokers, and non-smokers. Although walking was associated with a reduction in prevalence compared to the Inactive group, this reduction is smaller than in the higher PALs. Conversely, the Active or Very Active groups were associated with higher prevalences of positive SPH, being higher than the prevalences of positive SPH of Walkers, and these, in turn, were higher than the prevalences of Inactive.Physical inactivity increases the risks of having a negative SPH, regardless of the relationship with smoking, compared to walking or higher PALs. Walking may be sufficient to reduce the odds of having a negative HPS in inactive populations. However, walking increases the risk compared to moderate and/or intense PA populations.


Vitamin D deficiency and insufficiency as well as low serum calcium levels can trigger negative health outcomes in women of childbearing age. Therefore, we aimed to estimate the prevalence of serum vitamin D and calcium deficiencies and insufficiencies and associated risk factors in Brazilian women of childbearing age and to assess whether there are differences in prevalence according to regions of the country and the presence or absence of pregnancy. The systematic literature review was performed using the following databases: PubMed, LILACS, Embase, Scopus, and Web of Science. Cross-sectional, cohort, and intervention studies were included. Among pregnant women, the prevalence of vitamin D deficiency ranged from 0% to 27% and of vitamin D insufficiency from 33.9% to 70.4%. Among non-pregnant women, the prevalence of vitamin D deficiency ranged from 0% to 41.7% and of vitamin D insufficiency from 38.5% to 69.3%. We found a high prevalence of vitamin D deficiency and insufficiency in women of childbearing age, with insufficiency affecting more than half of these women. The highest prevalence of vitamin D deficiency and insufficiency was observed in the South region. It was not possible to assess the prevalence and factors associated with calcium deficiency. Nutritional deficiencies affect individuals worldwide , especiaIn an observational study conducted in Southern Korea, 89% of women of childbearing age had low concentrations of vitamin D , and anoThe evidence showing that vitamin D deficiency can trigger negative outcomes for both the mother and child, including hypertension in women of childbearing age , gestatiVitamin D is a hormone that can regulate calcium metabolism . CalciumDespite the importance of this topic, there is only one systematic review conducted in Brazil on the prevalence of vitamin D deficiency and insufficiency . Our revPrevalence of vitamin D and calcium deficiencies and their health impacts on women of childbearing age: a protocol for systematic review and meta-analysis [This systematic review and meta-analysis were conducted in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) protocols. This review follows the PICO structure, with “P” (population) being women of childbearing age, “I” being no intervention, “C” being comparison between pregnant and non-pregnant subgroups and region, and “O” (outcome) being the prevalence calcium and vitamin D deficiency. The protocol (CRD42020207850) of this systematic review was registered on the PROSPERO platform and published under the title analysis .The systematic literature review was performed using the following databases: PubMed , LILACS , Embase, Scopus, and Web of Science. The search was conducted in December 2021 to identify articles published until that date for inclusion in this review. The review was updated in March 2022. The search strategy included relevant keywords related to vitamin D deficiency and specific terms related to calcium deficiency to ensure that all articles of interest were identified. Details describing the entire methodology and search strategy with the terms are published in the protocol article .Studies that provide data on the prevalence of serum calcium and/or vitamin D deficiency in women of childbearing age (15–49 years or menarche and menopause).Studies with representative population-based samples in hospitals, health centers, or outpatient clinics.Prevalence data in women of different age groups, such as adolescents, pregnant women, lactating women, and premenopausal adult women.Studies with a cross-sectional design and data from longitudinal studies (cohort studies) or intervention studies, such as clinical trials or community trials, provided they had prevalence information for a specific time. Articles in English, Portuguese, and Spanish were included.○Opinion articles, comments, or editorials.○Duplicate articles, i.e., the same study found in different databases.○Articles with the same database/population/sample, in which case the study with the largest sample size was considered.○Articles with primary data not accessible even after request to the authors.○Case-control articles, narrative reviews, and case series.○Studies conducted among female athletes of any sport.○Studies conducted among women with the following specific diseases: autoimmune diseases such as lupus, psoriasis, thyroiditis, rheumatoid arthritis, and multiple sclerosis; eating disorders such as anorexia and bulimia; hematological diseases such as thalassemia and sickle cell disease; respiratory diseases such as chronic obstructive pulmonary disease, asthma, pneumonia, respiratory infections, and tuberculosis; chronic diseases such as heart failure, kidney failure, liver disease, chronic kidney disease, heart disease, nephrotic syndrome, AIDS, inflammatory bowel disease, hypo- or hyperthyroidism, sepsis, and cancer; genetic diseases and syndromes such as vitamin D receptor mutation, cystic fibrosis, and Prader–Willi syndrome; neurological or psychiatric disorders such as epilepsy (or antiepileptic medication use), attention deficit hyperactivity disorder, and schizophrenia.○Studies conducted among post-surgical patients, patients with trauma or burns, or patients undergoing recent treatment for fractures or orthopedic/osteoarticular diseases.○Studies conducted among patients undergoing intensive, urgency or emergency, or palliative care.○Studies with fewer than 50 participants.○Studies conducted among indigenous women.The authors responsible for assessing the eligibility criteria of the articles were trained. An eligibility test was performed with 50 titles and abstracts before coding the articles. The reviewers also received training in the instruments used to assess the risk of bias through five articles that were not included in the review. Rayyan and Mendeley software were used for the selection steps, the first being the selection of studies and the second being the exclusion of duplicate articles.After completing the search strategy, the identified articles were gathered and imported into the Mendeley software. Duplicate articles were excluded. The articles were selected by two independent reviewers (L.A.N.M. and M.C.R.C.). The titles were read first and then the abstracts. Finally, the entire article was read. Disagreements between the two reviewers were resolved by a third reviewer (E.A.S.). Eligibility was determined according to inclusion and exclusion criteria.Data were extracted using a table considering the following aspects: author/year, type of study, study location, age group, sample type/sample size, place of residence , gestational status (yes/no), lactating (yes/no), micronutrients analyzed, technique used, cut-off points and results—that is, prevalence/impact of calcium or vitamin D deficiency. The values of vitamin D are expressed as nanogram per milliliter (ng/mL) or nanol per liter (nmol/L). For conversion purposes, it is enough to multiply ng/mL by 2.5 to obtain the value in nmol/L .The Downs and Black scale used to assess the risk of bias is an instrument with 27 items, but with only 16 items being applicable to observational studies . The score was applied to each article according to the number of items, considering the total percentage (0 to 17 points). Low risk of bias was defined as a total score > 70%.The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence of selected studies. For each study, quality was assigned one of the following four grades: high quality (four filled circles), moderate quality (three filled circles), low quality (two filled circles), or very low quality (one filled circle).Data were extracted and evaluated by two independent reviewers (L.A.N.M. and M.C.R.C.). Disagreements were resolved by a third reviewer (E.A.S.). A researcher (M.C.R.C.) contacted the authors of the articles to obtain relevant data not reported in their article. Potential conflicts of interest and ethical information from the studies included in the review were also reported.A meta-analysis was performed to assess the prevalence of vitamin D deficiency and insufficiency in Brazilian women. The analyses were stratified by region of the country and pregnancy status (pregnant or non-pregnant). Given the high heterogeneity between studies, random-effects models were used to reduce differences. We calculated the mean of the vitamin D deficiency and/or prevalence values stratified by gestational trimester in the studies and pooled them for meta-analysis. The analyses were performed using the R language (version 4.1.0) and the Meta package (version 6.0-0) and metaprop command. When the analyses included more than ten publications, a funnel plot was used to assess the asymmetry between studies.Of the 149 articles with data on serum calcium and vitamin D deficiency and insufficiency in Brazilian women of childbearing age initially identified in the databases, 143 articles remained after the exclusion of duplicates. After applying the eligibility criteria, 73 articles were selected for full reading, of which 16 were included in the systematic review. Seven articles provided information on pregnant women of which five provided information on serum vitamin D and two on calcium .The number of women in studies that evaluated vitamin D in pregnant women ranged from 174 to 487, and they were aged between 20 and 40 years, with only two studies including adolescents .The number of non-pregnant women ranged from 15 to 369, with eight studies having a sample of fewer than 100. Five studies included only adolescents, and seven included adult women or adults and adolescents. The number of women in the two studies that evaluated calcium ranged from 99 to 226, and the age range varied between 16 and 44 years of age .Most studies were conducted in the Southeast (six articles) and South (four articles) regions. Only two studies were conducted in the Midwest region, and none were conducted in the North region. The cut-off points for both pregnant and non-pregnant women varied widely in the assessment of vitamin D deficiency and insufficiency, with the lowest value for deficiency being ≤10 ng/mL and the highest being <20 ng/mL.Among pregnant women, the prevalence of vitamin D deficiency ranged from 0% to 27% and the prevalence of insufficiency ranged from 33.9% to 70.4%. One study considered the prevalence of both deficiency and insufficiency in pregnant women, which reached 82.9%. Among non-pregnant women, the prevalence of deficiency ranged from 0% to 41.7% and the prevalence of insufficiency ranged from 38.52% to 69.3%. Two articles reported the prevalence of both insufficiency and deficiency in non-pregnant women, which reached 74.1%.The factors associated with the risk of vitamin D deficiency in pregnant women were being married, the use of vehicles as a means of transportation, blood collection in winter, only face and hands being exposed to the sun, preeclampsia, first pregnancy, adolescence, and low income ,34. HoweThe hypocalcemia cut-off values ranged from <8.6 to <8.8 mg/dL and only one article with pregnant women showed a 15% prevalence of deficiency .The Downs and Black scale scores ranged from 54% to 100% . FourteeI2: 99%) and 29% in non-pregnant women , while the overall prevalence was 29% . The analysis of deficiency by region , with no differences between pregnant and non-pregnant women. A higher prevalence of vitamin D insufficiency was observed in the South region than in the other regions, although the confidence intervals did not show significant differences  and non-pregnant (29.4%) women without significant differences. The prevalence of insufficiency was 59% and it was similar between pregnant and non-pregnant women. It was not possible to perform a meta-analysis of the studies that estimated the prevalence of calcium deficiency due to the small number of studies, i.e., only two articles. Similarly, we could not conduct a meta-analysis to identify the risk factors associated with vitamin D and calcium deficiency and insufficiency due to the heterogeneity of the investigated factors and the reduced number of studies.The overall prevalence of vitamin D deficiency (29%) and insufficiency (59%) identified in this meta-analysis were slightly higher than those found in an observational study conducted in Colombia that found a 24% prevalence of vitamin D deficiency and a 47% prevalence of vitamin D insufficiency . An obseAnother influencing factor is the dietary intake of vitamin D, whose levels show a statistically positive association with the Mediterranean diet, regardless of body mass index . The aveThe meta-analysis by Brazilian geographic regions showed that the prevalence of vitamin D deficiency and insufficiency was higher in the South region. A possible explanation for this is that the South region has a subtropical climate and, due to its proximity to the Tropic of Capricorn, it is characterized by the lowest temperatures in the country. The main source of vitamin D in humans is UVB radiation (290–315 nm) from the sun on the skin , and expIt is important to highlight that we did not find studies conducted in the North region of Brazil, which is characterized by pockets of poverty and the worst indicators of infant mortality and health in the country. Only one study in the Midwest region and three in the North region described regional inequalities, not only from the socioeconomic point of view but also from the perspective of promotion of scientific research.Vitamin D deficiency cut-offs varied widely in the studies included in this review. This is in line with a systematic review including 33 observational studies that showed wide variations in the cut-off values used by studies to determine vitamin D deficiency . The pubThe risk factors most associated with vitamin D deficiency in pregnant women in the studies included were being married, the use of vehicles, sun exposure of only the face and hands, preeclampsia, and low income. Being married was identified as a risk factor for vitamin D deficiency in an observational study in Saudi Arabia , whereasA possible limitation of this study was that most of the articles showing vitamin D deficiency and insufficiency were conducted in the Southeast and South regions of the country (63%), which can be considered a bias with respect to obtaining an overview of the country. In most of the articles included in this systematic review, women who supplemented vitamin D were excluded from the study samples ,46,47,48This study highlights the high prevalence of vitamin D insufficiency in both pregnant and non-pregnant women. Thus, we highlight the need for the development of public policies, with a focus on preventing and minimizing this problem. From the point of view of clinical implication, national health education campaigns, focusing on behavioral measures such as 10 minutes of daily sun exposure and a balanced diet ,75 as weThe education on and promotion of health, including dietary intake that meets nutrient and micronutrient needs, with the use of supplementation and food fortification if necessary, may constitute policies to improve nutritional deficiencies in general ,58,76. HAccording to the Brazilian Society of Endocrinology and Metabology, the diagnosis of serum vitamin D deficiency should be performed in pregnant and lactating women . ConsideThis systematic review and meta-analysis showed a high prevalence of vitamin D deficiency and a higher prevalence of vitamin D insufficiency in Brazilian women of childbearing age. There was no significant difference between pregnant and non-pregnant women. We found a higher prevalence of vitamin D deficiency and insufficiency in the South region. It was not possible to carry out a meta-analysis of calcium deficiency, as only two articles addressed the topic, with one presenting only its prevalence and the other just the mean serum calcium levels.This systematic review revealed a wide variability in the cut-off points used to classify vitamin D deficiency and insufficiency. Therefore, the results demonstrate the importance of standardizing cut-off points to facilitate comparisons between studies and to obtain accurate and reproducible information about the prevalence of vitamin D deficiency and insufficiency. Considering that vitamin D deficiency and insufficiency was common in women of childbearing age in Brazil, public health policies aimed at primary healthcare should be conducted with a focus on preventing vitamin D insufficiency in this population.


The outcome was the occurrence of myocardial infarction (MI) or stroke. MI was defined as one hospitalization or two outpatient visits with ICD-10-CM codes I21 or I22. Stroke was defined as one hospitalization with ICD-10-CM codes I63 or I64 and a claim for brain imaging (CT or MRI). The Cox proportional hazard model and Kaplan–Meier curve were used for analysis. The mean follow-up duration was 4.7 years, and the incidence rate of CVD was higher in the RA group than the control group . The risk of MI and stroke was about 50% and 20% higher, respectively, in RA patients. The association between RA and CVD was prominent in females after adjusting for confounding variables. The association between RA and risk of MI was significant in individuals without DM. Therefore, appropriate screening for CVD is important in all RA patients including females and younger patients.Despite a growing burden posed by cardiovascular disease (CVD) in rheumatoid arthritis (RA) patients, large-scale studies on the association between the characteristics of RA patients and CVD risks and studies adjusted for various confounding factors are lacking. In this large-scale nationwide cohort study, we aimed to investigate the association between CVD risk and RA and factors that may increase CVD risk using a dataset provided by the Korean National Health Insurance Service (NHIS). We enrolled 136,469 patients with RA who participated in national health examinations within two years of RA diagnosis between 2010 and 2017 and non-RA controls matched by age and sex ( Rheumatoid arthritis (RA) is a systemic inflammatory disease with high mortality and morbidity rates that are mainly attributable to cardiovascular disease (CVD) . RA is cSeveral epidemiologic studies have investigated the association between CVD risk and RA. Previous cohort studies conducted in western countries reported that RA was linked to a higher risk of CVD, with a 1.4- to 3.7-fold increased risk for myocardial infarction (MI) and 1.3- to 2.7-fold increased risk for stroke ,12,13,14In contrast to data showing increased risk of MI among RA patients ,6,9,10, To date, accumulating evidence has revealed that incident CV risk is higher in RA patients compared with the general population. However, the extent of the increase in CV risk differs among studies, and which characteristics of RA patients are mainly associated with increased CV risk remains unclear. Among studies to date, the largest sample size was 114,342 subjects, but the study only included female subjects and used self-reported questionnaires to define RA, CVD, and other covariates . UnfortuThe study used a dataset provided by the National Health Insurance Service (NHIS) in Republic of Korea. The NHIS is an insurance provider managed by the government that covers 97% of the population, approximately 50 million people. The NHIS dataset includes information on socioeconomic, demographic variables, health care utilization, health examination findings, disease diagnosis under the ICD-10 Clinical Modification (ICD-10-CM), and medical treatment and procedure. NHIS offers a standardized health examination at least every two years . The NHIn = 286,906). Among them, patients who underwent a health examination within two years before the first diagnosis of RA and were matched by age and sex to individuals without RA (using a 1:5 ratio) were included. RA was defined as at least one claim under ICD-10-CM code M05 or M06 and at least one claim for prescription of any DMARD. The validity of these algorithms was evaluated in previous studies, which found a positive predictive value > 0.82 [We included adults over the age of 19 with a diagnosis of RA between 1 January 2010 and 31 December 2017 , with any missing variables of interest. We also excluded patients with a diagnosis of MI or stroke before enrollment to increase the accuracy of primary endpoint diagnosis. A history of MI or stroke was defined using ICD-10-CM codes  regardless of admission. This study protocol followed the Declaration of Helsinki and was approved by the Institutional Review Board of Samsung Medical Center (IRB File No. SMC 2021-12-083). This study did not require informed consent because no identifiable patient information was available to researchers.2. Through the health examination, body weight, waist circumference, and blood pressure were measured, and laboratory test items such as fasting glucose, total cholesterol, and creatinine were included. From the self-reported questionnaire, demographic and lifestyle data were collected, including data of smoking, alcohol, and regular exercise. Smoking status was divided as smoker (current smokers) and nonsmoker (never and ex-smokers). Subjects with an intake ≥30 g of alcohol per day were classified as heavy alcohol drinkers. Regular exercise was defined as moderate physical activity for ≥30 min at least five times per week or vigorous physical activity for ≥20 min at least three times per week. Income level was classified into the lowest 20% of income. These definitions were based on previous studies [The date of diagnosis of RA was defined as the index date. The index date of controls was defined as the RA diagnosis date of their matched counterpart. Baseline comorbidities such as hypertension, diabetes, and hyperlipidemia were collected based on the combination of health examination results and ICD-10-CM diagnosis and prescription information. Hypertension was defined as systolic/diastolic BP ≥ 140/90 mmHg, ICD code I10–13 or I15, and claims for antihypertensive medication prescription. Diabetes was defined as at least one claim of the E11–14 code and at least one antidiabetic medication prescription or a fasting plasma glucose level ≥ 126 mg/dL. Hyperlipidemia was defined as E78 code and at least one prescription claim of lipid-lowering medication or serum total cholesterol level ≥240 mg/dL. Chronic kidney disease was defined as estimated glomerular filtration rate <60 mL/min/1.73 m studies .The endpoint of the study was newly diagnosed CVD. MI was defined as an ICD-10-CM code of I21 or I22 with one hospitalization. The validity of this definition was evaluated in prior studies with a positive predictive value (PPV) of 92% . Stroke p value less than 0.05 was considered statistically significant.Data were statistically analyzed using SAS version 9.4 . The baseline characteristics of the study population are presented as mean ± standard deviation (SD) for continuous variables, and categorical variables are expressed as numbers and percentages. The incidence rates of MI and stroke were calculated by dividing the number of incident events by the total follow-up period (1000 person-years). Hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of incident CVD were calculated by the Cox proportional hazard model. In multivariable analysis, the following confounders were adjusted: age, sex, smoking, alcohol drinking, regular exercise, obesity, DM, HTN, hyperlipidemia, CKD, and income. In addition to multivariable analysis, propensity score matching (PSM) analysis was adopted to adjust for disparities in baseline characteristics between the RA and non-RA cohorts. Selection bias can be reduced using PSM . Kaplan–The datasets generated during the current study are available from the corresponding author upon reasonable request.Of the 286,906 subjects with newly diagnosed RA (≥19 years of age) in the dataset, there were 286,148 RA subjects with age- and sex-matched counterparts, and 161,335 RA subjects with examined health check-up 2 years before the index date. After applying the exclusion criteria, 136,469 RA subjects were included in the analysis. A total of 683,345 age- and sex-matched individuals was analyzed as controls. The flowchart of the study population selection is shown in In the original cohort, baseline characteristics were significantly different between RA and non-RA groups . Thus, tp for interaction < 0.0001; stroke: aHR 2.35 in <40 years, 1.22 in 40–64 years, 1.21 in ≥65 years, p for interaction = 0.0100). Similarly, we observed a significant association between MI and RA in females. The association of stroke with RA was pronounced in females . The association between RA and risk of MI was significant in individuals without DM .Stratified analysis on the association of RA with the risk of stroke and MI was performed based on various factors and the results are given in p = 0.02). However, they defined RA and CVD according to self-reported questionnaires, in contrast to our study that used validated criteria [In this large-scale study, RA was associated with increased risk of MI and stroke after adjusting for various confounders. Compared with subjects without RA, subjects with RA had 54% and 23% increases in the risk of MI and stroke, respectively. The results were similar after applying for PSM. The current results confirm those obtained in previous studies. In a 2012 meta-analysis, there was a 48% increased risk of incident CVD in RA subjects ; the increased risks of MI and stroke were 68%  and 41% , respectively . The extcriteria ,16. The criteria .The origin of excess risk and extent of the contribution of risk factors in RA cohorts have been major questions over the past decades . The incSystemic inflammation has been recognized as a central mechanism in the development of CVD, and this inflammatory response modulates other CVD risk factors, resulting in a special association between CV risk and RA compared with the general population . Pro-infSome studies failed to demonstrate increased stroke risk in RA, but our study confirmed that the risk of ischemic stroke was higher in RA. This might be explained by the difference in stroke definition used in studies. Despite a discrepant risk factor profile and different pathogenesis between ischemic stroke and hemorrhagic stroke, some studies defined stroke using composite outcomes that included both ischemic and hemorrhagic stroke ,23. Consp < 0.003). This suggests that CV risk under current risk algorithms developed for the general populations is especially underestimated in younger RA patients [In the subgroup analysis, there were significant interactions with age in the association between RA and CVD outcomes. The associations of RA with MI and stroke were stronger in the younger age group. The HRs of both events were highest in younger individuals with RA. However, as expected, absolute events increased with age. This suggests that RA might also be an important risk factor of major CVD, especially in younger individuals. The findings were similar to those obtained in a previous meta-analysis. The results of the meta-analysis revealed that, compared with the general population, the relative risks for CVD events in RA subjects are highest for younger patients, whereas older RA patients had a similar relative risk to age-matched controls  . A Nijmepatients . A Britipatients .These risk patterns suggest several possible explanations. This finding highlights the concept of competing risk: as the population ages, relatively rare risk factors (such as RA) for CVD have less of an impact than other common risk factors. Hence, the rate ratio attributable to RA seems smaller with increasing age . AnotherIn the current study, there were significant interactions with sex in the association between RA and major CVD events. The increased risk of MI and stroke associated with RA was prominent in women. This result is not unique. In previous studies, CVD has been recognized as a more common disease in women than men . One posSome interesting results arose from the subgroup analyses. The incident rate of MI was higher in individuals with DM, both in the RA group and control group. However, the association of RA and MI was significantly higher in non-DM individuals than in DM individuals. A possible explanation is that the direct contribution of systemic inflammation attributable to RA may be higher in non-DM patients than those with DM. In other words, the role of diabetes related to MI may be very potent, and the relative contribution of RA is smaller among DM patients. Therefore, a preventative strategy of MI in RA patients should be emphasized regardless of DM.Our study has a few limitations. First, PSM was applied and possible confounders were included in the multivariable model, but the possibility of unmeasured residual confounding factors cannot be excluded, and family history of CVD was not included. Moreover, additional statistical analysis such as nested case–control or risk set sampling was impossible in this study because of the characteristics of the NHIS database. Second, given the retrospective observational nature of the study, our findings cannot be used to prove a causal relationship. Third, we could not consider the severity of RA related to inflammation status because we did not have information on inflammatory markers such as C-reactive protein or disease activity score such as DAS-28, which are not collected in NIHS data. We also did not analyze the use of arthritis medications. Arthritis drugs are associated with CVD risk because they not only improve inflammation, but can also have adverse effects on CVD. Therefore, arthritis medication analysis would help elucidate CVD patterns and prevention in RA patients. Future research is warranted on the drug effects related to CVD. However, our study is meaningful because it identified the characteristics that affect the development of CVD in RA patients using a large population-based cohort that is representative of the demographic characteristics of the South Korea population. It also adjusted for various confounders and used a validated algorithm to define variables. We adopted PSM to minimize selection bias, which was not used in previous cohort studies. Data completeness without missing participants or variables of interest during a long-term follow-up period further strengthened this research, and stratified analysis yielded several interesting findings.In conclusion, we found that RA was an important risk factor for the development of CVD. In particular, the association between CVD and RA was greater in females and younger individuals. The association between ischemic stroke and RA was significant in non-DM patients. These study findings indicate that more integrated and targeted CV prevention strategies will be important to help mitigate CVD risk in RA populations.