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      Identifying Risk Indicators of Cardiovascular Disease in Fasa Cohort Study (FACS): An Application of Generalized Linear Mixed-Model Tree

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          Abstract

          Background:

          Today, cardiovascular disease (CVD) is the most important cause of death around the world. In this study, our main aim was to predict CVD using some of the most important indicators of this disease and present a tree-based statistical framework for detecting CVD patients according to these indicators.

          Methods:

          We used data from the baseline phase of the Fasa Cohort Study (FACS). The outcome variable was the presence of CVD. The ordinary Tree and generalized linear mixed models (GLMM) were fitted to the data and their predictive power for detecting CVD was compared with the obtained results from the GLMM tree. Statistical analysis was performed using the RStudio software.

          Results:

          Data of 9499 participants aged 35‒70 years were analyzed. The results of the multivariable mixed-effects logistic regression model revealed that participants’ age, total cholesterol, marital status, smoking status, glucose, history of cardiac disease or myocardial infarction (MI) in first- and second-degree relatives, and presence of other diseases (like hypertension, depression, chronic headaches, and thyroid disease) were significantly related to the presence of CVD ( P<0.05). Fitting the ordinary tree, GLMM, and GLMM tree resulted in area under the curve (AUC) values of 0.58 (0.56, 0.61), 0.81 (0.77, 0.84), and 0.80 (0.76, 0.83), respectively, among the study population. In addition, the tree model had the best specificity at 81% but the lowest sensitivity at 65% compared to the other models.

          Conclusion:

          Given the superior performance of the GLMM tree compared with the standard tree and the lack of significant difference with the GLMM, using this model is suggested due to its simpler interpretation and fewer assumptions. Using updated statistical models for more accurate CVD prediction can result in more precise frameworks to aid in proactive patient detection planning.

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          Most cited references43

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          Heart Disease and Stroke Statistics—2015 Update: A Report From the American Heart Association

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            Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms

            Hypertension and type 2 diabetes are common comorbidities. Hypertension is twice as frequent in patients with diabetes compared with those who do not have diabetes. Moreover, patients with hypertension often exhibit insulin resistance and are at greater risk of diabetes developing than are normotensive individuals. The major cause of morbidity and mortality in diabetes is cardiovascular disease, which is exacerbated by hypertension. Accordingly, diabetes and hypertension are closely interlinked because of similar risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodelling, atherosclerosis, dyslipidemia, and obesity. There is also substantial overlap in the cardiovascular complications of diabetes and hypertension related primarily to microvascular and macrovascular disease. Common mechanisms, such as upregulation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, and activation of the immune system likely contribute to the close relationship between diabetes and hypertension. In this article we discuss diabetes and hypertension as comorbidities and discuss the pathophysiological features of vascular complications associated with these conditions. We also highlight some vascular mechanisms that predispose to both conditions, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs. Finally, we provide some insights into current therapies targeting diabetes and cardiovascular complications and introduce some new agents that may have vasoprotective therapeutic potential in diabetes.
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              High Blood Pressure and Cardiovascular Disease

              Fragmented investigation has masked the overall picture for causes of cardiovascular disease (CVD). Among the risk factors for CVD, high blood pressure (BP) is associated with the strongest evidence for causation and it has a high prevalence of exposure. Biologically, normal levels of BP are considerably lower than what has typically been characterized as normal in research and clinical practice. We propose that CVD is primarily caused by a right-sided shift in the population distribution of BP. Our view that BP is the predominant risk factor for CVD is based on conceptual postulates that have been tested in observational investigations and clinical trials. Large cohort studies have demonstrated that high BP is an important risk factor for heart failure, atrial fibrillation, chronic kidney disease, heart valve diseases, aortic syndromes, and dementia, in addition to coronary heart disease and stroke. In multivariate modeling, the presumed attributable risk of high BP for stroke and coronary heart disease has increased steadily with progressive use of lower values for normal BP. Meta-analysis of BP-lowering randomized controlled trials has demonstrated a benefit which is almost identical to that predicted from BP risk relationships in cohort studies. Prevention of age-related increases in BP would, in large part, reduce the vascular consequences usually attributed to aging, and together with intensive treatment of established hypertension would eliminate a large proportion of the population burden of BP-related CVD.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SoftwareRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: Project administrationRole: ValidationRole: Writing – original draft
                Role: Data curationRole: Investigation
                Role: SoftwareRole: Writing – original draftRole: Writing – review & editing
                Role: InvestigationRole: Writing – original draft
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: SupervisionRole: ValidationRole: Writing – original draftRole: Writing – review & editing
                Journal
                Arch Iran Med
                Arch Iran Med
                Arch Iran Med
                AIM
                Archives of Iranian Medicine
                Academy of Medical Sciences of I.R. Iran
                1029-2977
                1735-3947
                May 2024
                01 May 2024
                : 27
                : 5
                : 239-247
                Affiliations
                1Department of Biostatistics, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                2National Nutrition and Food Technology Research Institute, Faculty of Nutrition Sciences and Food Technology, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                3Noncommunicable diseases research center, Fasa University of Medical Sciences, Fasa, Iran
                4Statistical Center of Iran, Tehran, Iran
                5Proteomics Research Center and Department of Biostatistics, School of Allied Medical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
                Author notes
                [* ] Corresponding Author: Farid Zayeri, Email: fzayeri@ 123456gmail.com
                Author information
                https://orcid.org/0000-0003-1909-7001
                https://orcid.org/0000-0002-7791-8122
                Article
                10.34172/aim.2024.35
                11097325
                38690790
                80a2b256-b424-4392-8f3f-4191b517f8ea
                © 2024 The Author(s).

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 03 December 2023
                : 11 March 2024
                Categories
                Original Article

                cardiovascular diseases,fasa cohort study,glmm tree,mixed-effect model

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