Metabolite profiling and cardiovascular event risk: A prospective study of 3 population-based cohorts

Circulation

Volumn 131, Issue 9, 2015, Pages 774-785

  Würtz, Peter ^a,b,c   Havulinna, Aki S ^b,c   Soininen, Pasi ^a,d   Tynkkynen, Tuulia ^a,d   Prieto Merino, David ^e   Tillin, Therese ^f   Ghorbani, Anahita ^g   Artati, Anna ^h   Wang, Qin ^a,d   Tiainen, Mika ^a,d   Kangas, Antti J ^a   Kettunen, Johannes ^a,b   Kaikkonen, Jari ⁱ   Mikkilä, Vera ^c,i   Jula, Antti ^b   Kähönen, Mika ^j   Lehtimäki, Terho ^j   Lawlor, Debbie A ^k   Gaunt, Tom R ^k   Hughes, Alun D ^f   Sattar, Naveed ^l   Illig, Thomas ^h,m   Adamski, Jerzy ^h,n,o   Wang, Thomas J ^p,q   Perola, Markus ^b,c   Ripatti, Samuli ^c,r   Vasan, Ramachandran S ^g   Raitakari, Olli T ^i,p,s   Gerszten, Robert E ^e,t   Casas, Juan Pablo ^f   Chaturvedi, Nish ^f   Ala Korpela, Mika ^a,d,k,u   Salomaa, Veikko ^b   more..

^a UNIVERSITY OF OULU   (Finland)

^b NATIONAL PUBLIC HEALTH INSTITUTE   (Finland)

^c UNIVERSITY OF HELSINKI   (Finland)

^d UNIVERSITY OF EASTERN FINLAND   (Finland)

^e LONDON SCHOOL OF HYGIENE AND TROPICAL MEDICINE   (United Kingdom)

^f UNIVERSITY COLLEGE LONDON   (United Kingdom)

^g BOSTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^h INSTITUTE OF EPIDEMIOLOGY   (Germany)

ⁱ UNIVERSITY OF TURKU   (Finland)

^j TAMPERE UNIVERSITY OF TECHNOLOGY   (Finland)

^k UNIVERSITY OF BRISTOL   (United Kingdom)

^l UNIVERSITY OF GLASGOW   (United Kingdom)

^m HANNOVER MEDICAL SCHOOL   (Germany)

ⁿ GERMAN CENTER FOR DIABETES RESEARCH DZD   (Germany)

^o TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^p HARVARD MEDICAL SCHOOL   (United States)

^q VANDERBILT UNIVERSITY   (United States)

^r WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

^s TURKU UNIVERSITY HOSPITAL   (Finland)

^t BROAD INSTITUTE OF MIT AND HARVARD   (United States)

^u OULU UNIVERSITY HOSPITAL   (Finland)

more..

Author keywords

Amino acids; Biological markers; Fatty acids; Metabolomics; Risk factors

Indexed keywords

BIOLOGICAL MARKER; DOCOSAHEXAENOIC ACID; HIGH DENSITY LIPOPROTEIN; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; INTERMEDIATE DENSITY LIPOPROTEIN; LOW DENSITY LIPOPROTEIN; MONOUNSATURATED FATTY ACID; OMEGA 6 FATTY ACID; PHENYLALANINE; POLYUNSATURATED FATTY ACID; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN; CARDIOVASCULAR AGENT;

ADULT; AGED; ARTICLE; BLOOD PRESSURE; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; CHOLESTEROL BLOOD LEVEL; CLINICAL ARTICLE; COHORT ANALYSIS; DIABETES MELLITUS; FEMALE; FOLLOW UP; HUMAN; MALE; MASS SPECTROMETRY; METABOLITE; METABOLOMICS; NUCLEAR MAGNETIC RESONANCE; OBSERVATIONAL STUDY; PRIORITY JOURNAL; PROSPECTIVE STUDY; RISK ASSESSMENT; SEX DIFFERENCE; SMOKING; SYSTOLIC BLOOD PRESSURE; TRIACYLGLYCEROL BLOOD LEVEL; ADOLESCENT; AGE DISTRIBUTION; BLOOD; CARDIOVASCULAR DISEASES; CHILD; COMORBIDITY; ENDOPHENOTYPE; FINLAND; GREAT BRITAIN; HEALTH SURVEY; HIGH THROUGHPUT SCREENING; MIDDLE AGED; PROCEDURES; RISK FACTOR; SEX RATIO; UNITED STATES; VALIDATION STUDY; YOUNG ADULT;

ADOLESCENT; ADULT; AGE DISTRIBUTION; AGED; BIOMARKERS; BLOOD PRESSURE; CARDIOVASCULAR AGENTS; CARDIOVASCULAR DISEASES; CHILD; COMORBIDITY; DIABETES MELLITUS; DOCOSAHEXAENOIC ACIDS; ENDOPHENOTYPES; FATTY ACIDS, MONOUNSATURATED; FATTY ACIDS, OMEGA-6; FEMALE; FINLAND; GREAT BRITAIN; HEALTH SURVEYS; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MALE; MASS SPECTROMETRY; METABOLOMICS; MIDDLE AGED; NUCLEAR MAGNETIC RESONANCE, BIOMOLECULAR; PHENYLALANINE; PROSPECTIVE STUDIES; RISK ASSESSMENT; RISK FACTORS; SEX DISTRIBUTION; SMOKING; UNITED STATES; YOUNG ADULT;

EID: 84929429714     PISSN: 00097322     EISSN: 15244539     Source Type: Journal    
DOI: 10.1161/CIRCULATIONAHA.114.013116     Document Type: Article

References (49)

1. Wang TJ. Assessing the role of circulating, genetic, and imaging biomarkers in cardiovascular risk prediction. Circulation. 2011;123:551-565.
2. Lloyd-Jones DM. Cardiovascular risk prediction: basic concepts, current status, and future directions. Circulation. 2010;121:1768-1777.
3. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, Goldberg AC, Gordon D, Levy D, Lloyd-Jones DM, McBride P, Schwartz JS, Shero ST, Smith SC Jr, Watson K, Wilson PW, Eddleman KM, Jarrett NM, LaBresh K, Nevo L, Wnek J, Anderson JL, Halperin JL, Albert NM, Bozkurt B, Brindis RG, Curtis LH, DeMets D, Hochman JS, Kovacs RJ, Ohman EM, Pressler SJ, Sellke FW, Shen WK, Smith SC Jr, Tomaselli GF. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129(25 suppl 2):S1-45.
4. Lipid modification: cardiovascular risk assessment and the modification of blood lipids for the primary and secondary prevention of cardiovascular disease. NICE guidelines [CG181]. London, UK: National Institute for Health and Care Excellence; July 2014. http://www.nice.org.uk/guidance/cg181. Accessed September 4, 2014.
5. Quehenberger O, Dennis EA. The human plasma lipidome. N Engl J Med. 2011;365:1812-1823.
6. Shah SH, Kraus WE, Newgard CB. Metabolomic profiling for the identification of novel biomarkers and mechanisms related to common cardiovascular diseases: form and function. Circulation. 2012;126:1110-1120.
7. Wang Z, Klipfell E, Bennett BJ, Koeth R, Levison BS, Dugar B, Feldstein AE, Britt EB, Fu X, Chung YM, Wu Y, Schauer P, Smith JD, Allayee H, Tang WH, DiDonato JA, Lusis AJ, Hazen SL. Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature. 2011;472:57-63.
8. Soininen P, Kangas AJ, Würtz P, Suna T, Ala-Korpela M. Quantitative serum nuclear magnetic resonance metabolomics in cardiovascular epidemiology and genetics. Circ Cardiov Genet. 2015. In press. doi: 10.1161/CIRCGENETICS.114.000216.
9. Inouye M, Kettunen J, Soininen P, Silander K, Ripatti S, Kumpula LS, Hämäläinen E, Jousilahti P, Kangas AJ, Männistö S, Savolainen MJ, Jula A, Leiviskä J, Palotie A, Salomaa V, Perola M, Ala-Korpela M, Peltonen L. Metabonomic, transcriptomic, and genomic variation of a population cohort. Mol Syst Biol. 2010;6:1-10.
10. Würtz P, Raiko JR, Magnussen CG, Soininen P, Kangas AJ, Tynkkynen T, Thomson R, Laatikainen R, Savolainen MJ, Laurikka J, Kuukasjärvi P, Tarkka M, Karhunen PJ, Jula A, Viikari JS, Kähönen M, Lehtimäki T, Juonala M, Ala-Korpela M, Raitakari OT. High-throughput quantification of circulating metabolites improves prediction of subclinical atherosclerosis. Eur Heart J. 2012;33:2307-2316.
11. Tang WH, Wang Z, Levison BS, Koeth RA, Britt EB, Fu X, Wu Y, Hazen SL. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N Engl J Med. 2013;368:1575-1584.
12. Stegemann C, Pechlaner R, Willeit P, Langley SR, Mangino M, Mayr U, Menni C, Moayyeri A, Santer P, Rungger G, Spector TD, Willeit J, Kiechl S, Mayr M. Lipidomics profiling and risk of cardiovascular disease in the prospective population-based Bruneck study. Circulation. 2014;129:1821-1831.
13. Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011;17:448-453.
14. Rhee EP, Cheng S, Larson MG, Walford GA, Lewis GD, McCabe E, Yang E, Farrell L, Fox CS, O'Donnell CJ, Carr SA, Vasan RS, Florez JC, Clish CB, Wang TJ, Gerszten RE. Lipid profiling identifies a triacylglycerol signature of insulin resistance and improves diabetes prediction in humans. J Clin Invest. 2011;121:1402-1411.
15. Floegel A, Stefan N, Yu Z, Mühlenbruch K, Drogan D, Joost HG, Fritsche A, Häring HU, Hrabě de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes. 2013; 62:639-648.
16. Stančáková A, Civelek M, Saleem NK, Soininen P, Kangas AJ, Cederberg H, Paananen J, Pihlajamäki J, Bonnycastle LL, Morken MA, Boehnke M, Pajukanta P, Lusis AJ, Collins FS, Kuusisto J, Ala-Korpela M, Laakso M. Hyperglycemia and a common variant of GCKR are associated with the levels of eight amino acids in 9,369 Finnish men. Diabetes. 2012;61:1895-1902.
17. Mahendran Y, Cederberg H, Vangipurapu J, Kangas AJ, Soininen P, Kuusisto J, Uusitupa M, Ala-Korpela M, Laakso M. Glycerol and fatty acids in serum predict the development of hyperglycemia and type 2 diabetes in Finnish men. Diabetes Care. 2013;36:3732-3738.
18. Roberts LD, Gerszten RE. Toward new biomarkers of cardiometabolic diseases. Cell Metab. 2013;18:43-50.
19. Rankin NJ, Preiss D, Welsh P, Burgess KEV, Nelson SE, Lawlor DA, Sattar N. The emergence of proton nuclear magnetic resonance metabolomics in the cardiovascular arena as viewed from a clinical perspective. Atherosclerosis. 2014;237:287-300.
20. Kettunen J, Tukiainen T, Sarin AP, Ortega-Alonso A, Tikkanen E, Lyytikäinen LP, Kangas AJ, Soininen P, Würtz P, Silander K, Dick DM, Rose RJ, Savolainen MJ, Viikari J, Kähönen M, Lehtimäki T, Pietiläinen KH, Inouye M, McCarthy MI, Jula A, Eriksson J, Raitakari OT, Salomaa V, Kaprio J, Järvelin MR, Peltonen L, Perola M, Freimer NB, Ala- Korpela M, Palotie A, Ripatti S. Genome-wide association study identifies multiple loci influencing human serum metabolite levels. Nat Genet. 2012;44:269-76.
21. Auro K, Joensuu A, Fischer K, Kettunen J, Salo P, Mattsson H, Niironen M, Kaprio J, Eriksson JG, Lehtimäki T, Raitakari O, Jula A, Tiitinen A, Jauhiainen M, Soininen P, Kangas AJ, Kähönen M, Havulinna AS, Ala-Korpela M, Salomaa V, Metspalu A, Perola M. A metabolic view on menopause and aging. Nat Commun. 2014;5:4708.
22. Fischer K, Kettunen J, Würtz P, Haller T, Havulinna AS, Kangas AJ, Soininen P, Esko T, Tammesoo ML, Mägi R, Smit S, Palotie A, Ripatti S, Salomaa V, Ala-Korpela M, Perola M, Metspalu A. Biomarker profiling by nuclear magnetic resonance spectroscopy for the prediction of all-cause mortality: an observational study of 17,345 persons. PLoS Med. 2014;11:e1001606.
23. Ala-Korpela M, Kangas AJ, Soininen P. Quantitative high-throughput metabolomics: a new era in epidemiology and genetics. Genome Med. 2012;4:36.
24. Soininen P, Kangas AJ, Würtz P, Tukiainen T, Tynkkynen T, Laatikainen R, Järvelin MR, Kähönen M, Lehtimäki T, Viikari J, Raitakari OT, Savolainen MJ, Ala-Korpela M. High-throughput serum NMR metabonomics for cost-effective holistic studies on systemic metabolism. Analyst. 2009;134:1781-1785.
25. Griffin JL, Atherton H, Shockcor J, Atzori L. Metabolomics as a tool for cardiac research. Nat Rev Cardio. 2011;8:630-643.
26. Blankenberg S, Zeller T, Saarela O, Havulinna AS, Kee F, Tunstall-Pedoe H, Kuulasmaa K, Yarnell J, Schnabel RB, Wild PS, Münzel TF, Lackner KJ, Tiret L, Evans A, Salomaa V. Contribution of 30 biomarkers to 10-year cardiovascular risk estimation in 2 population cohorts. Circulation. 2010;121:2388-2397.
27. Vartiainen E, Laatikainen T, Peltonen M, Juolevi A, Männisto S, Sundvall J, Jousilahti P, Salomaa V, Valsta L, Puska P. Thirty-five-year trends in cardiovascular risk factors in Finland. Int J Epidemiol. 2010;39:504-518.
28. Pajunen P, Koukkunen H, Ketonen M, Jerkkola T, Immonen-Räihä P, Kärjä-Koskenkari P, Mähönen M, Niemelä M, Kuulasmaa K, Palomäki P, Mustonen J, Lehtonen A, Arstila M, Vuorenmaa T, Lehto S, Miettinen H, Torppa J, Tuomilehto J, Kesäniemi YA, Pyörälä K, Salomaa V. The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease. Eur J Cardiovasc Prev Rehabil. 2005;12:132-137.
29. Tillin T, Hughes AD, Mayet J, Whincup P, Sattar N, Forouhi NG, McKeigue PM, Chaturvedi N. The relationship between metabolic risk factors and incident cardiovascular disease in Europeans, South Asians, and African Caribbeans. J Am Coll Cardiol. 2013;61:1777-1786.
30. Lawlor DA, Bedford C, Taylor M, Ebrahim S. Geographical variation in cardiovascular disease, risk factors, and their control in older women: British Women's Heart and Health Study. J Epidemiol Community Health. 2003;57:134-140.
31. Kujala UM, Mäkinen VP, Heinonen I, Soininen P, Kangas AJ, Leskinen TH, Rahkila P, Würtz P, Kovanen V, Cheng S, Sipilä S, Hirvensalo M, Telama R, Tammelin T, Savolainen MJ, Pouta A, O'Reilly PF, MäntyselkäP, Viikari J, Kähönen M, Lehtimäki T, Elliott P, Vanhala MJ, Raitakari OT, Järvelin MR, Kaprio J, Kainulainen H, Ala-Korpela M. Long-term leisure-time physical activity and serum metabolome. Circulation. 2012;127:340-348.
32. Würtz P, Wang Q, Kangas AJ, Richmond RC, Skarp J, Tiainen M, Tynkkynen T, Soininen P, Havulinna AS, Kaakkinen M, Viikari JS, Savolainen M, Kähönen M, Lehtimäki T, Männistö S, Blankenberg S, Zeller T, Laitinen J, Pouta A, Mäntyselkä P, Vanhala M, Elliott P, Pietiläinen KH, Ripatti S, Salomaa V, Raitakari OT, Järvelin MR, Davey Smith D, Ala-Korpela M. Metabolic signatures of adiposity: Mendelian randomization analysis and effects of weight change. PLoS Med. 2014;11:e1001765.
33. Shin SY, Fauman EB, Petersen AK, Krumsiek J, Santos R, Huang J, Arnold M, Erte I, Forgetta V, Yang TP, Walter K, Menni C, Chen L, Vasquez L, Valdes AM, Hyde CL, Wang V, Ziemek D, Roberts P, Xi L, Grundberg E; Multiple Tissue Human Expression Resource (MuTHER) Consortium, Waldenberger M, Richards JB, Mohney RP, Milburn MV, John SL, Trimmer J, Theis FJ, Overington JP, Suhre K, Brosnan MJ, Gieger C, Kastenmüller G, Spector TD, Soranzo N. An atlas of genetic influences on human blood metabolites. Nat Genet. 2014;46:543-550.
34. Kaikkonen JE, Kresanov P, Ahotupa M, Jula A, Mikkilä V, Viikari JS, Kähönen M, Lehtimäki T, Raitakari OT. High serum n6 fatty acid proportion is associated with lowered LDL oxidation and inflammation: the Cardiovascular Risk in Young Finns Study. Free Radic Res. 2014;48:420-426.
35. Antolini L, Nam BH, D'Agostico RB. Inference on correlated discrimination measures in survival analysis: a nonparametric approach. Commun Statist Theory Meth. 2004;33:2117-2135.
36. Pencina MJ, D'Agostino RB Sr, D'Agostino RB Jr, Vasan RS. Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond. Stat Med. 2008;27:157-172.
37. Pencina MJ, D'Agostino RB Sr, Steyerberg EW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30:11-21.
38. Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, Guiducci C, Perola M, Jula A, Sinisalo J, Lokki ML, Nieminen MS, Melander O, Salomaa V, Peltonen L, Kathiresan S. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet. 2010;376:1393-1400.
39. Superko HR, Superko SM, Nasir K, Agatston A, Garrett BC. Omega-3 fatty acid blood levels: clinical significance and controversy. Circulation. 2013;128:2154-2161.
40. Chowdhury R, Warnakula S, Kunutsor S, Crowe F, Ward HA, Johnson L, Franco OH, Butterworth AS, Forouhi NG, Thompson SG, Khaw KT, Mozaffarian D, Danesh J, Di Angelantonio E. Association of dietary, circulating, and supplement fatty acids with coronary risk: a systematic review and meta-analysis. Ann Intern Med. 2014;160:398-406.
41. Wu JH, Lemaitre RN, King IB, Song X, Psaty BM, Siscovick DS, Mozaffarian D. Circulating omega-6 polyunsaturated Fatty acids and total and cause-specific mortality: the cardiovascular health study. Circulation. 2014;130:1245-1253.
42. Magnusson M, Lewis GD, Ericson U, Orho-Melander M, Hedblad B, Engström G, Ostling G, Clish C, Wang TJ, Gerszten RE, Melander O. A diabetes-predictive amino acid score and future cardiovascular disease. Eur Heart J. 2013;34:1982-1989.
43. Murr C, Grammer TB, Meinitzer A, Kleber ME, März W, Fuchs D. Immune activation and inflammation in patients with cardiovascular disease are associated with higher phenylalanine to tyrosine ratios: the Ludwigshafen Risk and Cardiovascular Health Study. J Amino Acids. 2014;2014:783730.
44. Kris-Etherton PM. AHA Science Advisory. Monounsaturated fatty acids and risk of cardiovascular disease. American Heart Association. Nutrition Committee. Circulation. 1999;100:1253-1258.
45. Liu J, Cinar R, Xiong K, Godlewski G, Jourdan T, Lin Y, Ntambi JM, Kunos G. Monounsaturated fatty acids generated via stearoyl CoA desaturase-1 are endogenous inhibitors of fatty acid amide hydrolase. Proc Natl Acad Sci U S A. 2013;110:18832-18837.
46. Rizos EC, Ntzani EE, Bika E, Kostapanos MS, Elisaf MS. Association between omega-3 fatty acid supplementation and risk of major cardiovascular disease events: a systematic review and meta-analysis. JAMA. 2012;308:1024-1033.
47. Risk and Prevention Study Collaborative Group. n-3 fatty acids in patients with multiple cardiovascular risk factors. N Engl J Med. 2013;368:1800-1808.
48. Mozaffarian D, Micha R, Wallace S. Effects on coronary heart disease of increasing polyunsaturated fat in place of saturated fat: a systematic review and meta-analysis of randomized controlled trials. PLoS Med. 2010;7:e1000252.
49. Harris WS, Mozaffarian D, Rimm E, Kris-Etherton P, Rudel LL, Appel LJ, Engler MM, Engler MB, Sacks F. Omega-6 fatty acids and risk for cardiovascular disease. Circulation. 2009;119:902-907.