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      The Relationship of Dietary Cholesterol with Serum Low-Density Lipoprotein Cholesterol and Confounding by Reverse Causality:The INTERLIPID Study

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          Abstract

          Aim: The positive relationship between dietary cholesterol and serum cholesterol has been questioned by a set of recent cohort studies. This study aimed to investigate how employment status and education years relate to the association between dietary cholesterol and serum low-density lipoprotein cholesterol (LDL-C) in a Japanese population.

          Methods: A population-based, random sample, cross-sectional study (INTERLIPID) was performed. Among 1,145 Japanese individuals aged 40–59 years, 106 were excluded because of special diets, use of lipid-lowering drugs, hormone replacement, and missing data, leaving 1,039 individuals (533 men and 506 women). Dietary cholesterol was assessed from four 24-h dietary recalls, and LDL-C was measured enzymatically with an autoanalyzer. A standard questionnaire inquired about employment status and education years.

          Results: In men, a 1 standard deviation (SD) higher dietary cholesterol was associated with 3.16 mg/dL lower serum LDL-C ( P = 0.009; unadjusted model). After adjustment for covariates, higher serum LDL-C was estimated per 1 SD higher intake of dietary cholesterol in nonemployed men [self-employed, homemakers, farmers, fishermen, and retired employees; β = +9.08, 95% confidence interval (CI) = +0.90–+17.27] and less educated men ( β = +4.46, 95% CI = −0.97–+9.90), whereas an inverse association was observed in employed men ( β = −3.02, 95% CI= −5.49–−0.54) and more educated men ( β = −3.66, 95% CI = −6.25–−1.07).

          Conclusions: In men who were nonemployed and less educated, a higher intake of dietary cholesterol was associated with elevated concentrations of serum LDL-C, whereas an inverse association was observed in men who were employed and more educated.

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          Most cited references51

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          Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data.

          To examine the association between cigarette smoking in adults and serum lipid and lipoprotein concentrations the results of 54 published studies were analysed. Overall, smokers had significantly higher serum concentrations of cholesterol (3.0%), triglycerides (9.1%), very low density lipoprotein cholesterol (10.4%), and low density lipoprotein cholesterol (1.7%) and lower serum concentrations of high density lipoprotein cholesterol (-5.7%) and apolipoprotein AI (-4.2%) compared with nonsmokers. Among non-smokers and light, moderate, and heavy smokers a significant dose response effect was present for cholesterol (0, 1.8, 4.3, and 4.5% respectively), triglycerides (0, 10.7, 11.5, and 18.0%), very low density lipoprotein cholesterol (0, 7.2, 44.4, and 39.0%), low density lipoprotein cholesterol (0, -1.1, 1.4, and 11.0%), high density lipoprotein cholesterol (0, -4.6, -6.3, and -8.9%), and apolipoprotein AI (0, -3.7 and -5.7% in non-smokers and light and heavy smokers). These dose response effects may provide new evidence for a causal relation between exposure to cigarette smoke and changes in serum lipid and lipoprotein concentrations whether as a direct result of physiological changes or of dietary changes induced by smoking. Adequate prospective data to estimate the excess risk of coronary artery disease existed only for cholesterol concentration. When that information was combined with data from the present study, and given that smokers as a group face an average overall excess risk of coronary artery disease of 70%, it was estimated that the observed increased serum cholesterol concentration in smokers may account for at least 9% of that excess risk. Furthermore, the dose response effect of smoking on serum cholesterol concentration suggests a gradient of increased absolute risk of coronary artery disease between light and heavy smokers.
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            Cancer mortality in the United States by education level and race.

            Although both race and socioeconomic status are well known to influence mortality patterns in the United States, few studies have examined the simultaneous influence of these factors on cancer incidence and mortality. We examined relationships among race, education level, and mortality from cancers of the lung, breast, prostate, colon and rectum, and all sites combined in contemporary US vital statistics. Age-adjusted cancer death rates (with 95% confidence intervals [CIs]) were calculated for 137,708 deaths among 119,376,196 individuals aged 25-64 years, using race and education information from death certificates and population denominator data from the US Bureau of the Census, for 47 states and Washington, DC, in 2001. Relative risk (RR) estimates were used to compare cancer death rates in persons with 12 or fewer years of education with those in persons with more than 12 years of education. Educational attainment was strongly and inversely associated with mortality from all cancers combined in black and white men and in white women. The all-cancer death rates were nearly identical for black men and white men with 0-8 years of education (224.2 and 223.6 per 100,000, respectively). The estimated relative risk for all-cancer mortality comparing the three lowest ( 12 years) education categories was 2.38 (95% CI = 2.33 to 2.43) for black men, 2.24 (95% CI = 2.23 to 2.26) for white men, 1.43 (95% CI = 1.41 to 1.46) for black women, and 1.76 (95% CI = 1.75 to 1.78) for white women. For both men and women, the magnitude of the relative risks comparing the three lowest educational levels with the three highest within each race for all cancers combined and for lung and colorectal cancers was higher than the magnitude of the relative risks associated with race within each level of education, whereas for breast and prostate cancer the magnitude of the relative risks associated with race was higher than the magnitude of the relative risks associated with level of education within each racial group. Among the most important and novel findings were that black men who completed 12 or fewer years of education had a prostate cancer death rate that was more than double that of black men with more schooling (10.5 versus 4.8 per 100,000 men; RR = 2.17, 95% CI = 1.82 to 2.58) and that, in contrast with studies of mortality rates in earlier time periods, breast cancer mortality rates were higher among women with less education than among women with more education (37.0 and 31.1 per 100,000, respectively, for black women and 25.2 versus 18.6 per 100,000, respectively, for white women). Cancer death rates vary considerably by level of education. Identifying groups at high risk of death from cancer by level of education as well as by race may be useful in targeting interventions and tracking cancer disparities.
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              Egg consumption and risk of coronary heart disease and stroke: dose-response meta-analysis of prospective cohort studies

              Objective To investigate and quantify the potential dose-response association between egg consumption and risk of coronary heart disease and stroke. Design Dose-response meta-analysis of prospective cohort studies. Data sources PubMed and Embase prior to June 2012 and references of relevant original papers and review articles. Eligibility criteria for selecting studies Prospective cohort studies with relative risks and 95% confidence intervals of coronary heart disease or stroke for three or more categories of egg consumption. Results Eight articles with 17 reports (nine for coronary heart disease, eight for stroke) were eligible for inclusion in the meta-analysis (3 081 269 person years and 5847 incident cases for coronary heart disease, and 4 148 095 person years and 7579 incident cases for stroke). No evidence of a curve linear association was seen between egg consumption and risk of coronary heart disease or stroke (P=0.67 and P=0.27 for non-linearity, respectively). The summary relative risk of coronary heart disease for an increase of one egg consumed per day was 0.99 (95% confidence interval 0.85 to 1.15; P=0.88 for linear trend) without heterogeneity among studies (P=0.97, I2=0%). For stroke, the combined relative risk for an increase of one egg consumed per day was 0.91 (0.81 to 1.02; P=0.10 for linear trend) without heterogeneity among studies (P=0.46, I2=0%). In a subgroup analysis of diabetic populations, the relative risk of coronary heart disease comparing the highest with the lowest egg consumption was 1.54 (1.14 to 2.09; P=0.01). In addition, people with higher egg consumption had a 25% (0.57 to 0.99; P=0.04) lower risk of developing hemorrhagic stroke. Conclusions Higher consumption of eggs (up to one egg per day) is not associated with increased risk of coronary heart disease or stroke. The increased risk of coronary heart disease among diabetic patients and reduced risk of hemorrhagic stroke associated with higher egg consumption in subgroup analyses warrant further studies.
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                Author and article information

                Journal
                J Atheroscler Thromb
                J. Atheroscler. Thromb
                jat
                jat
                Journal of Atherosclerosis and Thrombosis
                Japan Atherosclerosis Society
                1340-3478
                1880-3873
                1 February 2019
                : 26
                : 2
                : 170-182
                Affiliations
                [1 ] Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Shiga, Japan
                [2 ] Department of Public Health, Shiga University of Medical Science, Shiga, Japan
                [3 ] Department of Food Science and Human Nutrition, Faculty of Agriculture, Ryukoku University, Kyoto, Japan
                [4 ] Department of Health and Nutrition, University of Human Arts and Sciences, Saitama, Japan
                [5 ] Department of Epidemiology and Public Health, Kanazawa Medical University, Kanazawa, Japan
                [6 ] Department of Hygiene and Preventive Medicine, Iwate Medical University, Iwate, Japan
                [7 ] School of Health Sciences, School of Medicine, Sapporo Medical University, Sapporo, Japan
                [8 ] Research Institute of Strategy for Prevention, Tokyo, Japan
                [9 ] Department of Food Science and Nutrition, Osaka City University, Osaka, Japan
                [10 ] Department of Epidemiology and Research, National Heart Foundation Hospital and Research Institute, Dhaka, Bangladesh
                [11 ] MRC-PHE Centre for Environment and Health, Department of Epidemiology and Biostatistics, Faculty of Medicine, School of Public Health, Imperial College London, London, UK
                [12 ] Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
                Author notes
                Address for correspondence: Yukiko Okami, Center for Epidemiological Research in Asia, Shiga University of Medical Science, Seta Tsukinowa-cho, Otsu-shi, Shiga 520-2192, Japan E-mail: okami@ 123456belle.shiga-med.ac.jp
                Article
                10.5551/jat.43075
                6365148
                29887537
                8aa19b00-58cf-4b30-a236-65bba1642a13
                2019 Japan Atherosclerosis Society

                This article is distributed under the terms of the latest version of CC BY-NC-SA defined by the Creative Commons Attribution License. http://creativecommons.org/licenses/by-nc-sa/3.0/

                History
                : 15 October 2017
                : 22 April 2018
                Page count
                Figures: 0, Tables: 4, References: 54, Pages: 13
                Categories
                Original Article

                cholesterol,employment,education,lifestyle modification,reverse causality

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