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      Association of physical activity, sedentary behaviours and sleep duration with cardiovascular diseases and lipid profiles: a Mendelian randomization analysis

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          Abstract

          Background

          Observational studies have shown that moderate-to-vigorous physical activity (MVPA), vigorous physical activity (VPA), sedentary behaviours, and sleep duration were associated with cardiovascular diseases (CVDs) and lipid levels. However, whether such observations reflect causality remain largely unknown. We aimed to investigate the causal associations of physical activity, sedentary behaviours, and sleep duration with coronary artery disease (CAD), myocardial infarction (MI), stroke and lipid levels.

          Methods

          We conducted a Mendelian randomization (MR) study using genetic variants as instruments which are associated with physical activity, sedentary behaviours, and sleep duration to examine the causal effects on CVDs and lipid levels. This study included analyses of 4 potentially modifiable factors and 7 outcomes. Thus, the threshold of statistical significance is P = 1.8 × 10 − 3 (0.05/4 × 7) after Bonferroni correction.

          Results

          In the present study, there was suggestive evidence for associations of genetically predicted VPA with CAD (odds ratio, 0.65; 95% confidence intervals, 0.47–0.90; P = 0.009) and MI (0.74; 0.59–0.93; P = 0.010). However, genetically predicted VPA, MVPA, sleep duration and sedentary behaviours did not show significant associations with stroke and any lipid levels.

          Conclusions

          Our findings from the MR approach provided suggestive evidence that vigorous exercise decreased risk of CAD and MI, but not stroke. However, there was no evidence to support causal associations of MVPA,sleep duration or sedentary behaviours with cardiovascular risk and lipid levels.

          Translational perspective

          The findings of this study did not point out specific recommendations on increasing physical activity required to deliver significant health benefits. Nevertheless, the findings allowed clinicians and public health practitioners to provide advice about increasing the total amount of excising time by demonstrating that such advice can be effective. Reliable assessment of the association of physical activity levels with different subtypes of CVDs is needed to provide the basis for a comprehensive clinical approach on CVDs prevention, which can be achieved through lifestyle interventions in addition to drug therapy.

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          Most cited references36

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          Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies.

          Aims To assess the relationship between duration of sleep and morbidity and mortality from coronary heart disease (CHD), stroke, and total cardiovascular disease (CVD). Methods and results We performed a systematic search of publications using MEDLINE (1966-2009), EMBASE (from 1980), the Cochrane Library, and manual searches without language restrictions. Studies were included if they were prospective, follow-up >3 years, had duration of sleep at baseline, and incident cases of CHD, stroke, or CVD. Relative risks (RR) and 95% confidence interval (CI) were pooled using a random-effect model. Overall, 15 studies (24 cohort samples) included 474 684 male and female participants (follow-up 6.9-25 years), and 16 067 events (4169 for CHD, 3478 for stroke, and 8420 for total CVD). Sleep duration was assessed by questionnaire and incident cases through certification and event registers. Short duration of sleep was associated with a greater risk of developing or dying of CHD (RR 1.48, 95% CI 1.22-1.80, P < 0.0001), stroke (1.15, 1.00-1.31, P = 0.047), but not total CVD (1.03, 0.93-1.15, P = 0.52) with no evidence of publication bias (P = 0.95, P = 0.30, and P = 0.46, respectively). Long duration of sleep was also associated with a greater risk of CHD (1.38, 1.15-1.66, P = 0.0005), stroke (1.65, 1.45-1.87, P < 0.0001), and total CVD (1.41, 1.19-1.68, P < 0.0001) with no evidence of publication bias (P = 0.92, P = 0.96, and P = 0.79, respectively). Conclusion Both short and long duration of sleep are predictors, or markers, of cardiovascular outcomes.
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            Recent Developments in Mendelian Randomization Studies

            Purpose of Review Mendelian randomization (MR) is a strategy for evaluating causality in observational epidemiological studies. MR exploits the fact that genotypes are not generally susceptible to reverse causation and confounding, due to their fixed nature and Mendel’s First and Second Laws of Inheritance. MR has the potential to provide information on causality in many situations where randomized controlled trials are not possible, but the results of MR studies must be interpreted carefully to avoid drawing erroneous conclusions. Recent Findings In this review, we outline the principles behind MR, as well as assumptions and limitations of the method. Extensions to the basic approach are discussed, including two-sample MR, bidirectional MR, two-step MR, multivariable MR, and factorial MR. We also consider some new applications and recent developments in the methodology, including its ability to inform drug development, automation of the method using tools such as MR-Base, and phenome-wide and hypothesis-free MR. Summary In conjunction with the growing availability of large-scale genomic databases, higher level of automation and increased robustness of the methods, MR promises to be a valuable strategy to examine causality in complex biological/omics networks, inform drug development and prioritize intervention targets for disease prevention in the future.
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              Exercise benefits in cardiovascular disease: beyond attenuation of traditional risk factors

              Despite strong scientific evidence supporting the benefits of regular exercise for the prevention and management of cardiovascular disease (CVD), physical inactivity is highly prevalent worldwide. In addition to merely changing well-known risk factors for systemic CVD, regular exercise can also improve cardiovascular health through non-traditional mechanisms. Understanding the pathways through which exercise influences different physiological systems is important and might yield new therapeutic strategies to target pathophysiological mechanisms in CVD. This Review includes a critical discussion of how regular exercise can have antiatherogenic effects in the vasculature, improve autonomic balance (thereby reducing the risk of malignant arrhythmias), and induce cardioprotection against ischaemia-reperfusion injury, independent of effects on traditional CVD risk factors. This Review also describes how exercise promotes a healthy anti-inflammatory milieu (largely through the release of muscle-derived myokines), stimulates myocardial regeneration, and ameliorates age-related loss of muscle mass and strength, a frequently overlooked non-traditional CVD risk factor. Finally, we discuss how the benefits of exercise might also occur via promotion of a healthy gut microbiota. We argue, therefore, that a holistic view of all body systems is necessary and useful when analysing the role of exercise in cardiovascular health.
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                Author and article information

                Contributors
                caoweihua60@163.com
                huangtaotao@pku.edu.cn
                Journal
                Lipids Health Dis
                Lipids Health Dis
                Lipids in Health and Disease
                BioMed Central (London )
                1476-511X
                8 May 2020
                8 May 2020
                2020
                : 19
                : 86
                Affiliations
                [1 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Department of Epidemiology & Biostatistics, School of Public Health, , Peking University, ; 38 Xueyuan Road, Bejing, 100191 China
                [2 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Institute of Reproductive and Child Health, , Peking University/Key Laboratory of Reproductive Health, National Health Commission of the People’s Republic of China, ; Bejing, 100191 China
                [3 ]GRID grid.194645.b, ISNI 0000000121742757, Department of Statistics and Actuarial Science, , The University of Hong Kong, ; Pok Fu Lam, Hong Kong
                [4 ]GRID grid.11135.37, ISNI 0000 0001 2256 9319, Department of Global Health, School of Public Health, , Peking University, ; Bejing, 100191 China
                [5 ]GRID grid.419897.a, ISNI 0000 0004 0369 313X, Key Laboratory of Molecular Cardiovascular Sciences (Peking University), Ministry of Education, ; Bejing, 100191 China
                Article
                1257
                10.1186/s12944-020-01257-z
                7206776
                32384904
                4d1bb7dc-b539-49de-b1bd-9db5d48f1e60
                © The Author(s) 2020

                Open AccessThis 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
                : 21 October 2019
                : 7 April 2020
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Biochemistry
                physical activity,cardiovascular diseases,mendelian randomization,causality
                Biochemistry
                physical activity, cardiovascular diseases, mendelian randomization, causality

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