Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study
Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and eve...
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| description | Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.
Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR |
| doi_str_mv | 10.1371/journal.pmed.1003410 |
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Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10-2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14-2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38-4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.
Evaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.</description><identifier>ISSN: 1549-1676</identifier><identifier>ISSN: 1549-1277</identifier><identifier>EISSN: 1549-1676</identifier><identifier>DOI: 10.1371/journal.pmed.1003410</identifier><identifier>PMID: 33275596</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Alcohol Drinking - adverse effects ; Alcohol Drinking - epidemiology ; Alcohol Drinking - genetics ; Alcohol use ; Alcoholic beverages ; Apolipoprotein B ; Beer ; Biology and Life Sciences ; Cardiovascular disease ; Cardiovascular diseases ; Cardiovascular Diseases - diagnosis ; Cardiovascular Diseases - epidemiology ; Cardiovascular Diseases - genetics ; Champagne ; Cholesterol ; Cider ; Consortia ; Coronary artery ; Coronary artery disease ; Coronary vessels ; Drinking of alcoholic beverages ; Epidemiology ; Genetic aspects ; Genetic Predisposition to Disease ; Genetics ; Genome-wide association studies ; Genome-Wide Association Study ; Genomes ; Genotype & phenotype ; Health aspects ; Heart Disease Risk Factors ; Heart diseases ; High density lipoprotein ; Humans ; Lipids ; Lipoproteins ; Low density lipoprotein ; Medicine and Health Sciences ; Mendelian Randomization Analysis ; Multivariate Analysis ; Phenotypes ; Polymorphism, Single Nucleotide ; Risk Assessment ; Risk factors ; Single-nucleotide polymorphism ; Smoking ; Social Sciences ; Stroke ; Tobacco ; Tobacco Use - adverse effects ; Tobacco Use - epidemiology ; Tobacco Use - genetics ; Triglycerides ; Wine</subject><ispartof>PLoS medicine, 2020-12, Vol.17 (12), p.e1003410</ispartof><rights>COPYRIGHT 2020 Public Library of Science</rights><rights>This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication: https://creativecommons.org/publicdomain/zero/1.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c764t-87695d0d68f671735c67e411d4884125b827b07a7324614d053076791332d6fd3</citedby><cites>FETCH-LOGICAL-c764t-87695d0d68f671735c67e411d4884125b827b07a7324614d053076791332d6fd3</cites><orcidid>0000-0002-0480-7755 ; 0000-0002-1407-8314</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717538/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717538/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2095,2914,23846,27903,27904,53769,53771,79346,79347</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33275596$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Gill, Dipender</contributor><creatorcontrib>Rosoff, Daniel B</creatorcontrib><creatorcontrib>Davey Smith, George</creatorcontrib><creatorcontrib>Mehta, Nehal</creatorcontrib><creatorcontrib>Clarke, Toni-Kim</creatorcontrib><creatorcontrib>Lohoff, Falk W</creatorcontrib><title>Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study</title><title>PLoS medicine</title><addtitle>PLoS Med</addtitle><description>Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.
Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10-2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14-2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38-4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.
Evaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.</description><subject>Alcohol Drinking - adverse effects</subject><subject>Alcohol Drinking - epidemiology</subject><subject>Alcohol Drinking - genetics</subject><subject>Alcohol use</subject><subject>Alcoholic beverages</subject><subject>Apolipoprotein B</subject><subject>Beer</subject><subject>Biology and Life Sciences</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular diseases</subject><subject>Cardiovascular Diseases - diagnosis</subject><subject>Cardiovascular Diseases - epidemiology</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Champagne</subject><subject>Cholesterol</subject><subject>Cider</subject><subject>Consortia</subject><subject>Coronary artery</subject><subject>Coronary artery disease</subject><subject>Coronary vessels</subject><subject>Drinking of alcoholic beverages</subject><subject>Epidemiology</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics</subject><subject>Genome-wide association studies</subject><subject>Genome-Wide Association Study</subject><subject>Genomes</subject><subject>Genotype & phenotype</subject><subject>Health aspects</subject><subject>Heart Disease Risk Factors</subject><subject>Heart diseases</subject><subject>High density lipoprotein</subject><subject>Humans</subject><subject>Lipids</subject><subject>Lipoproteins</subject><subject>Low density lipoprotein</subject><subject>Medicine and Health Sciences</subject><subject>Mendelian Randomization Analysis</subject><subject>Multivariate Analysis</subject><subject>Phenotypes</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Risk Assessment</subject><subject>Risk factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Smoking</subject><subject>Social Sciences</subject><subject>Stroke</subject><subject>Tobacco</subject><subject>Tobacco Use - adverse effects</subject><subject>Tobacco Use - epidemiology</subject><subject>Tobacco Use - genetics</subject><subject>Triglycerides</subject><subject>Wine</subject><issn>1549-1676</issn><issn>1549-1277</issn><issn>1549-1676</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>DOA</sourceid><recordid>eNqVk99qFDEUxgdRbK2-gWhAEIXumkxmkokXQilVC9WC_27D2eTMbkp2siYzq_UlfGWz223pyl4ouZjMye_7Tk4OpygeMzpmXLJXF2GIHfjxYo52zCjlFaN3in1WV2rEhBR3b-33igcpXVBaKqro_WKP81LWtRL7xe-TJfgBetdNST9DEtHnn9ClmVuQCfY_EDsC3oRZ8MTk-DBfrM4PSR8mYEwgQ8JDAp0lBqJ1YQnJDB4isS4hJHxNjsh88L1bQnQw8Ug-YGfRO-hIzLIwd7_WGUnqB3v5sLjXgk_4aPM9KL6-Pfly_H50dv7u9PjobGSkqPpRI4WqLbWiaYVkktdGSKwYs1XTVKysJ00pJ1SC5GUlWGVpzakUUrFcuRWt5QfF0yvfhQ9Jb94y6bJSlLOac5mJ0yvCBrjQi-jmEC91AKfXgRCnGmLvjEfNFW0UAEplZMVBKSu4qXhroC1No0T2erPJNkxyuwx2fQS_Zbp90rmZnoallrm4mjfZ4MXGIIbvA6Zez10y6D10GIbVvXOXmSpzgQfFs7_Q3dVtqCnkAlzXhpzXrEz1kahZ1Qgu6kyNdlBT7DBfMnTYuhze4sc7-Lwszp3ZKXi5JchMjz_7KQwp6dPPn_6D_fjv7Pm3bfb5LXaG4PtZCn5Yj8E2WF2BJoaUIrY3DWRUr2by-qX1aib1Ziaz7Mnt5t-IroeQ_wGEojEG</recordid><startdate>20201204</startdate><enddate>20201204</enddate><creator>Rosoff, Daniel B</creator><creator>Davey Smith, George</creator><creator>Mehta, Nehal</creator><creator>Clarke, Toni-Kim</creator><creator>Lohoff, Falk W</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISN</scope><scope>ISR</scope><scope>3V.</scope><scope>7TK</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><scope>CZK</scope><orcidid>https://orcid.org/0000-0002-0480-7755</orcidid><orcidid>https://orcid.org/0000-0002-1407-8314</orcidid></search><sort><creationdate>20201204</creationdate><title>Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study</title><author>Rosoff, Daniel B ; Davey Smith, George ; Mehta, Nehal ; Clarke, Toni-Kim ; Lohoff, Falk W</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c764t-87695d0d68f671735c67e411d4884125b827b07a7324614d053076791332d6fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Alcohol Drinking - adverse effects</topic><topic>Alcohol Drinking - epidemiology</topic><topic>Alcohol Drinking - genetics</topic><topic>Alcohol use</topic><topic>Alcoholic beverages</topic><topic>Apolipoprotein B</topic><topic>Beer</topic><topic>Biology and Life Sciences</topic><topic>Cardiovascular disease</topic><topic>Cardiovascular diseases</topic><topic>Cardiovascular Diseases - diagnosis</topic><topic>Cardiovascular Diseases - epidemiology</topic><topic>Cardiovascular Diseases - genetics</topic><topic>Champagne</topic><topic>Cholesterol</topic><topic>Cider</topic><topic>Consortia</topic><topic>Coronary artery</topic><topic>Coronary artery disease</topic><topic>Coronary vessels</topic><topic>Drinking of alcoholic beverages</topic><topic>Epidemiology</topic><topic>Genetic aspects</topic><topic>Genetic Predisposition to Disease</topic><topic>Genetics</topic><topic>Genome-wide association studies</topic><topic>Genome-Wide Association Study</topic><topic>Genomes</topic><topic>Genotype & phenotype</topic><topic>Health aspects</topic><topic>Heart Disease Risk Factors</topic><topic>Heart diseases</topic><topic>High density lipoprotein</topic><topic>Humans</topic><topic>Lipids</topic><topic>Lipoproteins</topic><topic>Low density lipoprotein</topic><topic>Medicine and Health Sciences</topic><topic>Mendelian Randomization Analysis</topic><topic>Multivariate Analysis</topic><topic>Phenotypes</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Risk Assessment</topic><topic>Risk factors</topic><topic>Single-nucleotide polymorphism</topic><topic>Smoking</topic><topic>Social Sciences</topic><topic>Stroke</topic><topic>Tobacco</topic><topic>Tobacco Use - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><collection>PLoS Medicine</collection><jtitle>PLoS medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rosoff, Daniel B</au><au>Davey Smith, George</au><au>Mehta, Nehal</au><au>Clarke, Toni-Kim</au><au>Lohoff, Falk W</au><au>Gill, Dipender</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study</atitle><jtitle>PLoS medicine</jtitle><addtitle>PLoS Med</addtitle><date>2020-12-04</date><risdate>2020</risdate><volume>17</volume><issue>12</issue><spage>e1003410</spage><pages>e1003410-</pages><issn>1549-1676</issn><issn>1549-1277</issn><eissn>1549-1676</eissn><abstract>Alcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.
Using large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04-0.47, P value = 1.72 × 10-28), triglycerides (TRG) (beta -0.23, 95% CI, -0.30, -0.15, P value = 4.69 × 10-10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03-0.18, P value = 4.72 × 10-3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03-0.16, P value = 5.24 × 10-3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014-0.027, P value = 6.59 × 10-12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03-1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01-1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01-1.03, P value = 5.56 × 10-4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10-6), CHD (OR = 1.64, 95% CI, 1.28-2.09, P value = 8.07 × 10-5), heart failure (HF) (OR = 1.61, 95% CI, 1.32-1.95, P value = 1.9 × 10-6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41-4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10-2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14-2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38-4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.
Evaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>33275596</pmid><doi>10.1371/journal.pmed.1003410</doi><orcidid>https://orcid.org/0000-0002-0480-7755</orcidid><orcidid>https://orcid.org/0000-0002-1407-8314</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1549-1676 |
| ispartof | PLoS medicine, 2020-12, Vol.17 (12), p.e1003410 |
| issn | 1549-1676 1549-1277 1549-1676 |
| language | eng |
| recordid | cdi_plos_journals_2490315337 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Alcohol Drinking - adverse effects Alcohol Drinking - epidemiology Alcohol Drinking - genetics Alcohol use Alcoholic beverages Apolipoprotein B Beer Biology and Life Sciences Cardiovascular disease Cardiovascular diseases Cardiovascular Diseases - diagnosis Cardiovascular Diseases - epidemiology Cardiovascular Diseases - genetics Champagne Cholesterol Cider Consortia Coronary artery Coronary artery disease Coronary vessels Drinking of alcoholic beverages Epidemiology Genetic aspects Genetic Predisposition to Disease Genetics Genome-wide association studies Genome-Wide Association Study Genomes Genotype & phenotype Health aspects Heart Disease Risk Factors Heart diseases High density lipoprotein Humans Lipids Lipoproteins Low density lipoprotein Medicine and Health Sciences Mendelian Randomization Analysis Multivariate Analysis Phenotypes Polymorphism, Single Nucleotide Risk Assessment Risk factors Single-nucleotide polymorphism Smoking Social Sciences Stroke Tobacco Tobacco Use - adverse effects Tobacco Use - epidemiology Tobacco Use - genetics Triglycerides Wine |
| title | Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study |
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