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      Effects of confounding and effect-modifying lifestyle, environmental and medical factors on risk of radiation-associated cardiovascular disease

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          Abstract

          Background

          Cardiovascular disease (CVD) is the leading cause of death worldwide. It has been known for some considerable time that radiation is associated with excess risk of CVD. A recent systematic review of radiation and CVD highlighted substantial inter-study heterogeneity in effect, possibly a result of confounding or modifications of radiation effect by non-radiation factors, in particular by the major lifestyle/environmental/medical risk factors and latent period.

          Methods

          We assessed effects of confounding by lifestyle/environmental/medical risk factors on radiation-associated CVD and investigated evidence for modifying effects of these variables on CVD radiation dose–response, using data assembled for a recent systematic review.

          Results

          There are 43 epidemiologic studies which are informative on effects of adjustment for confounding or risk modifying factors on radiation-associated CVD. Of these 22 were studies of groups exposed to substantial doses of medical radiation for therapy or diagnosis. The remaining 21 studies were of groups exposed at much lower levels of dose and/or dose rate. Only four studies suggest substantial effects of adjustment for lifestyle/environmental/medical risk factors on radiation risk of CVD; however, there were also substantial uncertainties in the estimates in all of these studies. There are fewer suggestions of effects that modify the radiation dose response; only two studies, both at lower levels of dose, report the most serious level of modifying effect.

          Conclusions

          There are still large uncertainties about confounding factors or lifestyle/environmental/medical variables that may influence radiation-associated CVD, although indications are that there are not many studies in which there are substantial confounding effects of these risk factors.

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          Most cited references123

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          A Proportional Hazards Model for the Subdistribution of a Competing Risk

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            Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study.

            Although more than 80% of the global burden of cardiovascular disease occurs in low-income and middle-income countries, knowledge of the importance of risk factors is largely derived from developed countries. Therefore, the effect of such factors on risk of coronary heart disease in most regions of the world is unknown. We established a standardised case-control study of acute myocardial infarction in 52 countries, representing every inhabited continent. 15152 cases and 14820 controls were enrolled. The relation of smoking, history of hypertension or diabetes, waist/hip ratio, dietary patterns, physical activity, consumption of alcohol, blood apolipoproteins (Apo), and psychosocial factors to myocardial infarction are reported here. Odds ratios and their 99% CIs for the association of risk factors to myocardial infarction and their population attributable risks (PAR) were calculated. Smoking (odds ratio 2.87 for current vs never, PAR 35.7% for current and former vs never), raised ApoB/ApoA1 ratio (3.25 for top vs lowest quintile, PAR 49.2% for top four quintiles vs lowest quintile), history of hypertension (1.91, PAR 17.9%), diabetes (2.37, PAR 9.9%), abdominal obesity (1.12 for top vs lowest tertile and 1.62 for middle vs lowest tertile, PAR 20.1% for top two tertiles vs lowest tertile), psychosocial factors (2.67, PAR 32.5%), daily consumption of fruits and vegetables (0.70, PAR 13.7% for lack of daily consumption), regular alcohol consumption (0.91, PAR 6.7%), and regular physical activity (0.86, PAR 12.2%), were all significantly related to acute myocardial infarction (p<0.0001 for all risk factors and p=0.03 for alcohol). These associations were noted in men and women, old and young, and in all regions of the world. Collectively, these nine risk factors accounted for 90% of the PAR in men and 94% in women. Abnormal lipids, smoking, hypertension, diabetes, abdominal obesity, psychosocial factors, consumption of fruits, vegetables, and alcohol, and regular physical activity account for most of the risk of myocardial infarction worldwide in both sexes and at all ages in all regions. This finding suggests that approaches to prevention can be based on similar principles worldwide and have the potential to prevent most premature cases of myocardial infarction.
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              Prediction of Coronary Heart Disease Using Risk Factor Categories

              The objective of this study was to examine the association of Joint National Committee (JNC-V) blood pressure and National Cholesterol Education Program (NCEP) cholesterol categories with coronary heart disease (CHD) risk, to incorporate them into coronary prediction algorithms, and to compare the discrimination properties of this approach with other noncategorical prediction functions. This work was designed as a prospective, single-center study in the setting of a community-based cohort. The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up. During the 12 years of follow-up, a total of 383 men and 227 women developed CHD, which was significantly associated with categories of blood pressure, total cholesterol, LDL cholesterol, and HDL cholesterol (all P or =130/85). The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol (> or =200 mg/dL) was 27% in men and 34% in women. Recommended guidelines of blood pressure, total cholesterol, and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample. A simple coronary disease prediction algorithm was developed using categorical variables, which allows physicians to predict multivariate CHD risk in patients without overt CHD.
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                Author and article information

                Contributors
                mark.little@nih.gov
                Journal
                BMC Public Health
                BMC Public Health
                BMC Public Health
                BioMed Central (London )
                1471-2458
                15 June 2024
                15 June 2024
                2024
                : 24
                : 1601
                Affiliations
                [1 ]Radiation Epidemiology Branch, National Cancer Institute, ( https://ror.org/040gcmg81) Room 7E546, 9609 Medical Center Drive MSC 9778, Bethesda, MD 20892-9778 USA
                [2 ]Faculty of Health and Life Sciences, Oxford Brookes University, ( https://ror.org/04v2twj65) Headington Campus, Oxford, OX3 0BP UK
                [3 ]Division of Radiation Health, University of Arkansas for Medical Sciences, ( https://ror.org/00xcryt71) Little Rock, AR USA
                [4 ]GRID grid.418735.c, ISNI 0000 0001 1414 6236, Institut de Radioprotection et de Sureté Nucléaire, ; Fontenay Aux Roses, France
                [5 ]Clinical Department, Southern Urals Biophysics Institute, Chelyabinsk Region, ( https://ror.org/03bw8s353) Ozyorskoe Shosse 19, Ozyorsk, 456780 Russia
                [6 ]GRID grid.266102.1, ISNI 0000 0001 2297 6811, Department of Epidemiology and Biostatistics, School of Medicine, , University of California San Francisco, ; 550 16th St 2nd floor, San Francisco, CA 94143 USA
                [7 ]Seymour, Paul, and Gloria Milstein Division of Cardiology, Department of Medicine, and Department of Radiology, Columbia University Irving Medical Center/New York-Presbyterian Hospital, ( https://ror.org/01esghr10) New York, NY USA
                [8 ]Biology and Environmental Chemistry Division, Sustainable System Research Laboratory, Central Research Institute of Electric Power Industry (CRIEPI), ( https://ror.org/041jswc25) 1646 Abiko, Chiba 270-1194, Japan
                Author information
                http://orcid.org/0000-0003-0980-7567
                http://orcid.org/0000-0003-2249-5203
                http://orcid.org/0000-0001-5807-4596
                http://orcid.org/0000-0001-6954-2674
                http://orcid.org/0000-0002-0778-1108
                http://orcid.org/0000-0003-2583-9278
                http://orcid.org/0000-0003-2518-6131
                Article
                18701
                10.1186/s12889-024-18701-9
                11179258
                38879521
                37ebf116-5358-4a49-93d1-e584a433160f
                © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2024

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 23 November 2023
                : 23 April 2024
                Categories
                Research
                Custom metadata
                © BioMed Central Ltd., part of Springer Nature 2024

                Public health
                cardiovascular disease,ionising radiation,heart disease,stroke,coronary heart disease,confounding

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