Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

Robert W. Tipping; Charles E. Ford; Lara M. Simpson; Göran Walldius; Ingmar Jungner; Aaron R. Folsom; Lloyd Chambless; Demosthenes Panagiotakos; Christos Pitsavos; Christina Chrysohoou; Christodoulos Stefanadis; Uri Goldbourt; Michal Benderly; David Tanne; Peter Whincup; S. Goya Wannamethee; Richard W. Morris; Stefan Kiechl; Johann Willeit; Peter Santer; Agnes Mayr; Nicholas Wald; Shah Ebrahim; Debbie Lawlor; John Yarnell; John Gallacher; Edoardo Casiglia; Valérie Tikhonoff; Paul J. Nietert; Susan E. Sutherland; David L. Bachman; Mary Cushman; Bruce M. Psaty; Russ Tracy; Anne Tybjærg-Hansen; Børge G. Nordestgaard; Ruth Frikke-Schmidt; Pia R. Kamstrup; Simona Giampaoli; Luigi Palmieri; Salvatore Panico; Diego Vanuzzo; Lorenza Pilotto; Agustín Gómez De La Cámara; Juan A. Gómez Gerique; Leon Simons; John McCallum; Yechiel Friedlander; F. Gerry R Fowkes; Amanda Lee; Felicity B. Smith; James Taylor; Jack M. Guralnik; Caroline L. Phillips; Robert B. Wallace; Dan G. Blazer; Hermann Brenner; Elke Raum; Heiko Müller; Dietrich Rothenbacher; Jan Håkan Jansson; Patrik Wennberg; Aulikki Nissinen; Chiara Donfrancesco; Veikko Salomaa; Kennet Harald; Pekka Jousilahti; Erkki Vartiainen; Mark Woodward; Ralph B. D’Agostino; Philip A. Wolf; Ramachandran S. Vasan; Michael J. Pencina; Else Marie Bladbjerg; Torben Jørgensen; Lars Møller; Jørgen Jespersen; Rachel Dankner; Angela Chetrit; Flora Lubin; Annika Rosengren; Lars Wilhelmsen; Georgios Lappas; Henry Eriksson; Cecilia Björkelund; Lauren Lissner; Calle Bengtsson; Peter Cremer; Dorothea Nagel; Reijo S. Tilvis; Timo E. Strandberg; Beatriz Rodriguez; Jacqueline Dekker; G. Nijpels; Coen D A Stehouwer; Eric Rimm; Jennifer K. Pai; Shinichi Sato; Hiroyasu Iso; Akihiko Kitamura; Hiroyuki Noda; Jukka T. Salonen; Kristiina Nyyssönen; Tomi Pekka Tuomainen; Dorly J H Deeg; Jan L. Poppelaars; Bo Hedblad; Göran Berglund; Gunnar Engström; W. M M Verschuren; Anneke Blokstra; Angela Döring; Wolfgang Koenig; Christa Meisinger; Wilfried Mraz; H. Bas Bueno-De-Mesquita; Lewis H. Kuller; Greg Grandits; Randi Selmer; Aage Tverdal; Wenche Nystad; R. F. Gillum; Michael Mussolino; Sue Hankinson; Jo Ann E Manson; Jackie A. Cooper; Kenneth A. Bauer; Yoshihiko Naito; Ingar Holme; Hideaki Nakagawa; Katsuyuki Miura; Pierre Ducimetiere; Xavier Jouven; Gérald Luc; Carlos J. Crespo; Mario R. Garcia Palmieri; Philippe Amouyel; Dominique Arveiler; Alun Evans; Jean Ferrieres; Helmut Schulte; Gerd Assmann; James Shepherd; Chris J. Packard; Naveed Sattar; Ian Ford; Bernard Cantin; Benoît Lamarche; Jean Pierre Després; Gilles R. Dagenais; Elizabeth Barrett-Connor; Lori B. Daniels; Gail A. Laughlin; Vilmundur Gudnason; Thor Aspelund; Gunnar Sigurdsson; Bolli Thorsson; Maurizio Trevisan; Jacqueline Witteman; Isabella Kardys; Monique M B Breteler; Albert Hofman; Hugh Tunstall-Pedoe; Roger Tavendale; Gordon Lowe; Yoav Ben-Shlomo; George Davey-Smith; Barbara V. Howard; Ying Zhang; Lyle Best; Jason Umans; Altan Onat; Inger Njølstad; Ellisiv B. Mathiesen; Maja Lisa Løchen; Tom Wilsgaard; Erik Ingelsson; Johan Sundström; Lars Lind; Lars Lannfelt; J. Michael Gaziano; Meir Stampfer; Paul M. Ridker; Hanno Ulmer; Günter Diem; Hans Concin; Alberto Tosetto; Francesco Rodeghiero; Michael Marmot; Robert Clarke; Rory Collins; Astrid Fletcher; Eric Brunner; Martin Shipley; Julie Buring; Stuart Cobbe; Michele Robertson; Yao He; Alejandro Marin Ibañez; Edith Feskens; Daan Kromhout; Matthew Walker; Sarah Watson; Emanuele Di Angelantonio; Sebhat Erqou; Stephen Kaptoge; Sarah Lewington; Lia Orfei; Lisa Pennells; Philip L. Perry; Kausik K. Ray; Nadeem Sarwar; Myriam Alexander; Alexander Thompson; Simon G. Thompson; Frances Wensley; Ian R. White; Angela M. Wood; John Danesh

doi:10.1001/jama.2009.1063

Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

Robert W. Tipping, Charles E. Ford, Lara M. Simpson, Göran Walldius, Ingmar Jungner, Aaron R. Folsom, Lloyd Chambless, Demosthenes Panagiotakos, Christos Pitsavos, Christina Chrysohoou, Christodoulos Stefanadis, Uri Goldbourt, Michal Benderly, David Tanne, Peter Whincup, S. Goya Wannamethee, Richard W. Morris, Stefan Kiechl, Johann Willeit, Peter SanterAgnes Mayr, Nicholas Wald, Shah Ebrahim, Debbie Lawlor, John Yarnell, John Gallacher, Edoardo Casiglia, Valérie Tikhonoff, Paul J. Nietert, Susan E. Sutherland, David L. Bachman, Mary Cushman, Bruce M. Psaty, Russ Tracy, Anne Tybjærg-Hansen, Børge G. Nordestgaard, Ruth Frikke-Schmidt, Pia R. Kamstrup, Simona Giampaoli, Luigi Palmieri, Salvatore Panico, Diego Vanuzzo, Lorenza Pilotto, Agustín Gómez De La Cámara, Juan A. Gómez Gerique, Leon Simons, John McCallum, Yechiel Friedlander, F. Gerry R Fowkes, Amanda Lee, Felicity B. Smith, James Taylor, Jack M. Guralnik, Caroline L. Phillips, Robert B. Wallace, Dan G. Blazer, Hermann Brenner, Elke Raum, Heiko Müller, Dietrich Rothenbacher, Jan Håkan Jansson, Patrik Wennberg, Aulikki Nissinen, Chiara Donfrancesco, Veikko Salomaa, Kennet Harald, Pekka Jousilahti, Erkki Vartiainen, Mark Woodward, Ralph B. D’Agostino, Philip A. Wolf, Ramachandran S. Vasan, Michael J. Pencina, Else Marie Bladbjerg, Torben Jørgensen, Lars Møller, Jørgen Jespersen, Rachel Dankner, Angela Chetrit, Flora Lubin, Annika Rosengren, Lars Wilhelmsen, Georgios Lappas, Henry Eriksson, Cecilia Björkelund, Lauren Lissner, Calle Bengtsson, Peter Cremer, Dorothea Nagel, Reijo S. Tilvis, Timo E. Strandberg, Beatriz Rodriguez, Jacqueline Dekker, G. Nijpels, Coen D A Stehouwer, Eric Rimm, Jennifer K. Pai, Shinichi Sato, Hiroyasu Iso, Akihiko Kitamura, Hiroyuki Noda, Jukka T. Salonen, Kristiina Nyyssönen, Tomi Pekka Tuomainen, Dorly J H Deeg, Jan L. Poppelaars, Bo Hedblad, Göran Berglund, Gunnar Engström, W. M M Verschuren, Anneke Blokstra, Angela Döring, Wolfgang Koenig, Christa Meisinger, Wilfried Mraz, H. Bas Bueno-De-Mesquita, Lewis H. Kuller, Greg Grandits, Randi Selmer, Aage Tverdal, Wenche Nystad, R. F. Gillum, Michael Mussolino, Sue Hankinson, Jo Ann E Manson, Jackie A. Cooper, Kenneth A. Bauer, Yoshihiko Naito, Ingar Holme, Hideaki Nakagawa, Katsuyuki Miura, Pierre Ducimetiere, Xavier Jouven, Gérald Luc, Carlos J. Crespo, Mario R. Garcia Palmieri, Philippe Amouyel, Dominique Arveiler, Alun Evans, Jean Ferrieres, Helmut Schulte, Gerd Assmann, James Shepherd, Chris J. Packard, Naveed Sattar, Ian Ford, Bernard Cantin, Benoît Lamarche, Jean Pierre Després, Gilles R. Dagenais, Elizabeth Barrett-Connor, Lori B. Daniels, Gail A. Laughlin, Vilmundur Gudnason, Thor Aspelund, Gunnar Sigurdsson, Bolli Thorsson, Maurizio Trevisan, Jacqueline Witteman, Isabella Kardys, Monique M B Breteler, Albert Hofman, Hugh Tunstall-Pedoe, Roger Tavendale, Gordon Lowe, Yoav Ben-Shlomo, George Davey-Smith, Barbara V. Howard, Ying Zhang, Lyle Best, Jason Umans, Altan Onat, Inger Njølstad, Ellisiv B. Mathiesen, Maja Lisa Løchen, Tom Wilsgaard, Erik Ingelsson, Johan Sundström, Lars Lind, Lars Lannfelt, J. Michael Gaziano, Meir Stampfer, Paul M. Ridker, Hanno Ulmer, Günter Diem, Hans Concin, Alberto Tosetto, Francesco Rodeghiero, Michael Marmot, Robert Clarke, Rory Collins, Astrid Fletcher, Eric Brunner, Martin Shipley, Julie Buring, Stuart Cobbe, Michele Robertson, Yao He, Alejandro Marin Ibañez, Edith Feskens, Daan Kromhout, Matthew Walker, Sarah Watson, Emanuele Di Angelantonio, Sebhat Erqou, Stephen Kaptoge, Sarah Lewington, Lia Orfei, Lisa Pennells, Philip L. Perry, Kausik K. Ray, Nadeem Sarwar, Myriam Alexander, Alexander Thompson, Simon G. Thompson, Frances Wensley, Ian R. White, Angela M. Wood, John Danesh

Research output: Contribution to journal › Review article › peer-review

1292 Scopus citations

Abstract

Context Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein–like particle, may be associated with risk of coronary heart disease (CHD) and stroke. Objective To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. Study Selection Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. Data Extraction Individual records were provided for each of 126 634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22 076 firstever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. Data Synthesis Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 personyears and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. Conclusion Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

Original language	English (US)
Pages (from-to)	412-423
Number of pages	12
Journal	JAMA
Volume	302
Issue number	4
DOIs	https://doi.org/10.1001/jama.2009.1063
State	Published - Jul 22 2009

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©2009 American Medical Association. All rights reserved.

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Tipping, R. W., Ford, C. E., Simpson, L. M., Walldius, G., Jungner, I., Folsom, A. R., Chambless, L., Panagiotakos, D., Pitsavos, C., Chrysohoou, C., Stefanadis, C., Goldbourt, U., Benderly, M., Tanne, D., Whincup, P., Wannamethee, S. G., Morris, R. W., Kiechl, S., Willeit, J., ... Danesh, J. (2009). Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA, 302(4), 412-423. https://doi.org/10.1001/jama.2009.1063

Tipping, RW, Ford, CE, Simpson, LM, Walldius, G, Jungner, I, Folsom, AR, Chambless, L, Panagiotakos, D, Pitsavos, C, Chrysohoou, C, Stefanadis, C, Goldbourt, U, Benderly, M, Tanne, D, Whincup, P, Wannamethee, SG, Morris, RW, Kiechl, S, Willeit, J, Santer, P, Mayr, A, Wald, N, Ebrahim, S, Lawlor, D, Yarnell, J, Gallacher, J, Casiglia, E, Tikhonoff, V, Nietert, PJ, Sutherland, SE, Bachman, DL, Cushman, M, Psaty, BM, Tracy, R, Tybjærg-Hansen, A, Nordestgaard, BG, Frikke-Schmidt, R, Kamstrup, PR, Giampaoli, S, Palmieri, L, Panico, S, Vanuzzo, D, Pilotto, L, De La Cámara, AG, Gómez Gerique, JA, Simons, L, McCallum, J, Friedlander, Y, Fowkes, FGR, Lee, A, Smith, FB, Taylor, J, Guralnik, JM, Phillips, CL, Wallace, RB, Blazer, DG, Brenner, H, Raum, E, Müller, H, Rothenbacher, D, Jansson, JH, Wennberg, P, Nissinen, A, Donfrancesco, C, Salomaa, V, Harald, K, Jousilahti, P, Vartiainen, E, Woodward, M, D’Agostino, RB, Wolf, PA, Vasan, RS, Pencina, MJ, Bladbjerg, EM, Jørgensen, T, Møller, L, Jespersen, J, Dankner, R, Chetrit, A, Lubin, F, Rosengren, A, Wilhelmsen, L, Lappas, G, Eriksson, H, Björkelund, C, Lissner, L, Bengtsson, C, Cremer, P, Nagel, D, Tilvis, RS, Strandberg, TE, Rodriguez, B, Dekker, J, Nijpels, G, Stehouwer, CDA, Rimm, E, Pai, JK, Sato, S, Iso, H, Kitamura, A, Noda, H, Salonen, JT, Nyyssönen, K, Tuomainen, TP, Deeg, DJH, Poppelaars, JL, Hedblad, B, Berglund, G, Engström, G, Verschuren, WMM, Blokstra, A, Döring, A, Koenig, W, Meisinger, C, Mraz, W, Bueno-De-Mesquita, HB, Kuller, LH, Grandits, G, Selmer, R, Tverdal, A, Nystad, W, Gillum, RF, Mussolino, M, Hankinson, S, Manson, JAE, Cooper, JA, Bauer, KA, Naito, Y, Holme, I, Nakagawa, H, Miura, K, Ducimetiere, P, Jouven, X, Luc, G, Crespo, CJ, Garcia Palmieri, MR, Amouyel, P, Arveiler, D, Evans, A, Ferrieres, J, Schulte, H, Assmann, G, Shepherd, J, Packard, CJ, Sattar, N, Ford, I, Cantin, B, Lamarche, B, Després, JP, Dagenais, GR, Barrett-Connor, E, Daniels, LB, Laughlin, GA, Gudnason, V, Aspelund, T, Sigurdsson, G, Thorsson, B, Trevisan, M, Witteman, J, Kardys, I, Breteler, MMB, Hofman, A, Tunstall-Pedoe, H, Tavendale, R, Lowe, G, Ben-Shlomo, Y, Davey-Smith, G, Howard, BV, Zhang, Y, Best, L, Umans, J, Onat, A, Njølstad, I, Mathiesen, EB, Løchen, ML, Wilsgaard, T, Ingelsson, E, Sundström, J, Lind, L, Lannfelt, L, Gaziano, JM, Stampfer, M, Ridker, PM, Ulmer, H, Diem, G, Concin, H, Tosetto, A, Rodeghiero, F, Marmot, M, Clarke, R, Collins, R, Fletcher, A, Brunner, E, Shipley, M, Buring, J, Cobbe, S, Robertson, M, He, Y, Ibañez, AM, Feskens, E, Kromhout, D, Walker, M, Watson, S, Di Angelantonio, E, Erqou, S, Kaptoge, S, Lewington, S, Orfei, L, Pennells, L, Perry, PL, Ray, KK, Sarwar, N, Alexander, M, Thompson, A, Thompson, SG, Wensley, F, White, IR, Wood, AM & Danesh, J 2009, 'Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality', JAMA, vol. 302, no. 4, pp. 412-423. https://doi.org/10.1001/jama.2009.1063

@article{18d80cca2cae4619b384c8cddd259a5f,

title = "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality",

abstract = "Context Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein–like particle, may be associated with risk of coronary heart disease (CHD) and stroke. Objective To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. Study Selection Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. Data Extraction Individual records were provided for each of 126 634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22 076 firstever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. Data Synthesis Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 personyears and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. Conclusion Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.",

author = "Tipping, {Robert W.} and Ford, {Charles E.} and Simpson, {Lara M.} and G{\"o}ran Walldius and Ingmar Jungner and Folsom, {Aaron R.} and Lloyd Chambless and Demosthenes Panagiotakos and Christos Pitsavos and Christina Chrysohoou and Christodoulos Stefanadis and Uri Goldbourt and Michal Benderly and David Tanne and Peter Whincup and Wannamethee, {S. Goya} and Morris, {Richard W.} and Stefan Kiechl and Johann Willeit and Peter Santer and Agnes Mayr and Nicholas Wald and Shah Ebrahim and Debbie Lawlor and John Yarnell and John Gallacher and Edoardo Casiglia and Val{\'e}rie Tikhonoff and Nietert, {Paul J.} and Sutherland, {Susan E.} and Bachman, {David L.} and Mary Cushman and Psaty, {Bruce M.} and Russ Tracy and Anne Tybj{\ae}rg-Hansen and Nordestgaard, {B{\o}rge G.} and Ruth Frikke-Schmidt and Kamstrup, {Pia R.} and Simona Giampaoli and Luigi Palmieri and Salvatore Panico and Diego Vanuzzo and Lorenza Pilotto and {De La C{\'a}mara}, {Agust{\'i}n G{\'o}mez} and {G{\'o}mez Gerique}, {Juan A.} and Leon Simons and John McCallum and Yechiel Friedlander and Fowkes, {F. Gerry R} and Amanda Lee and Smith, {Felicity B.} and James Taylor and Guralnik, {Jack M.} and Phillips, {Caroline L.} and Wallace, {Robert B.} and Blazer, {Dan G.} and Hermann Brenner and Elke Raum and Heiko M{\"u}ller and Dietrich Rothenbacher and Jansson, {Jan H{\aa}kan} and Patrik Wennberg and Aulikki Nissinen and Chiara Donfrancesco and Veikko Salomaa and Kennet Harald and Pekka Jousilahti and Erkki Vartiainen and Mark Woodward and D{\textquoteright}Agostino, {Ralph B.} and Wolf, {Philip A.} and Vasan, {Ramachandran S.} and Pencina, {Michael J.} and Bladbjerg, {Else Marie} and Torben J{\o}rgensen and Lars M{\o}ller and J{\o}rgen Jespersen and Rachel Dankner and Angela Chetrit and Flora Lubin and Annika Rosengren and Lars Wilhelmsen and Georgios Lappas and Henry Eriksson and Cecilia Bj{\"o}rkelund and Lauren Lissner and Calle Bengtsson and Peter Cremer and Dorothea Nagel and Tilvis, {Reijo S.} and Strandberg, {Timo E.} and Beatriz Rodriguez and Jacqueline Dekker and G. Nijpels and Stehouwer, {Coen D A} and Eric Rimm and Pai, {Jennifer K.} and Shinichi Sato and Hiroyasu Iso and Akihiko Kitamura and Hiroyuki Noda and Salonen, {Jukka T.} and Kristiina Nyyss{\"o}nen and Tuomainen, {Tomi Pekka} and Deeg, {Dorly J H} and Poppelaars, {Jan L.} and Bo Hedblad and G{\"o}ran Berglund and Gunnar Engstr{\"o}m and Verschuren, {W. M M} and Anneke Blokstra and Angela D{\"o}ring and Wolfgang Koenig and Christa Meisinger and Wilfried Mraz and Bueno-De-Mesquita, {H. Bas} and Kuller, {Lewis H.} and Greg Grandits and Randi Selmer and Aage Tverdal and Wenche Nystad and Gillum, {R. F.} and Michael Mussolino and Sue Hankinson and Manson, {Jo Ann E} and Cooper, {Jackie A.} and Bauer, {Kenneth A.} and Yoshihiko Naito and Ingar Holme and Hideaki Nakagawa and Katsuyuki Miura and Pierre Ducimetiere and Xavier Jouven and G{\'e}rald Luc and Crespo, {Carlos J.} and {Garcia Palmieri}, {Mario R.} and Philippe Amouyel and Dominique Arveiler and Alun Evans and Jean Ferrieres and Helmut Schulte and Gerd Assmann and James Shepherd and Packard, {Chris J.} and Naveed Sattar and Ian Ford and Bernard Cantin and Beno{\^i}t Lamarche and Despr{\'e}s, {Jean Pierre} and Dagenais, {Gilles R.} and Elizabeth Barrett-Connor and Daniels, {Lori B.} and Laughlin, {Gail A.} and Vilmundur Gudnason and Thor Aspelund and Gunnar Sigurdsson and Bolli Thorsson and Maurizio Trevisan and Jacqueline Witteman and Isabella Kardys and Breteler, {Monique M B} and Albert Hofman and Hugh Tunstall-Pedoe and Roger Tavendale and Gordon Lowe and Yoav Ben-Shlomo and George Davey-Smith and Howard, {Barbara V.} and Ying Zhang and Lyle Best and Jason Umans and Altan Onat and Inger Nj{\o}lstad and Mathiesen, {Ellisiv B.} and L{\o}chen, {Maja Lisa} and Tom Wilsgaard and Erik Ingelsson and Johan Sundstr{\"o}m and Lars Lind and Lars Lannfelt and Gaziano, {J. Michael} and Meir Stampfer and Ridker, {Paul M.} and Hanno Ulmer and G{\"u}nter Diem and Hans Concin and Alberto Tosetto and Francesco Rodeghiero and Michael Marmot and Robert Clarke and Rory Collins and Astrid Fletcher and Eric Brunner and Martin Shipley and Julie Buring and Stuart Cobbe and Michele Robertson and Yao He and Iba{\~n}ez, {Alejandro Marin} and Edith Feskens and Daan Kromhout and Matthew Walker and Sarah Watson and {Di Angelantonio}, Emanuele and Sebhat Erqou and Stephen Kaptoge and Sarah Lewington and Lia Orfei and Lisa Pennells and Perry, {Philip L.} and Ray, {Kausik K.} and Nadeem Sarwar and Myriam Alexander and Alexander Thompson and Thompson, {Simon G.} and Frances Wensley and White, {Ian R.} and Wood, {Angela M.} and John Danesh",

year = "2009",

month = jul,

day = "22",

doi = "10.1001/jama.2009.1063",

language = "English (US)",

volume = "302",

pages = "412--423",

journal = "JAMA",

issn = "0098-7484",

publisher = "American Medical Association",

number = "4",

}

TY - JOUR

T1 - Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

AU - Tipping, Robert W.

AU - Ford, Charles E.

AU - Simpson, Lara M.

AU - Walldius, Göran

AU - Jungner, Ingmar

AU - Folsom, Aaron R.

AU - Chambless, Lloyd

AU - Panagiotakos, Demosthenes

AU - Pitsavos, Christos

AU - Chrysohoou, Christina

AU - Stefanadis, Christodoulos

AU - Goldbourt, Uri

AU - Benderly, Michal

AU - Tanne, David

AU - Whincup, Peter

AU - Wannamethee, S. Goya

AU - Morris, Richard W.

AU - Kiechl, Stefan

AU - Willeit, Johann

AU - Santer, Peter

AU - Mayr, Agnes

AU - Wald, Nicholas

AU - Ebrahim, Shah

AU - Lawlor, Debbie

AU - Yarnell, John

AU - Gallacher, John

AU - Casiglia, Edoardo

AU - Tikhonoff, Valérie

AU - Nietert, Paul J.

AU - Sutherland, Susan E.

AU - Bachman, David L.

AU - Cushman, Mary

AU - Psaty, Bruce M.

AU - Tracy, Russ

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G.

AU - Frikke-Schmidt, Ruth

AU - Kamstrup, Pia R.

AU - Giampaoli, Simona

AU - Palmieri, Luigi

AU - Panico, Salvatore

AU - Vanuzzo, Diego

AU - Pilotto, Lorenza

AU - De La Cámara, Agustín Gómez

AU - Gómez Gerique, Juan A.

AU - Simons, Leon

AU - McCallum, John

AU - Friedlander, Yechiel

AU - Fowkes, F. Gerry R

AU - Lee, Amanda

AU - Smith, Felicity B.

AU - Taylor, James

AU - Guralnik, Jack M.

AU - Phillips, Caroline L.

AU - Wallace, Robert B.

AU - Blazer, Dan G.

AU - Brenner, Hermann

AU - Raum, Elke

AU - Müller, Heiko

AU - Rothenbacher, Dietrich

AU - Jansson, Jan Håkan

AU - Wennberg, Patrik

AU - Nissinen, Aulikki

AU - Donfrancesco, Chiara

AU - Salomaa, Veikko

AU - Harald, Kennet

AU - Jousilahti, Pekka

AU - Vartiainen, Erkki

AU - Woodward, Mark

AU - D’Agostino, Ralph B.

AU - Wolf, Philip A.

AU - Vasan, Ramachandran S.

AU - Pencina, Michael J.

AU - Bladbjerg, Else Marie

AU - Jørgensen, Torben

AU - Møller, Lars

AU - Jespersen, Jørgen

AU - Dankner, Rachel

AU - Chetrit, Angela

AU - Lubin, Flora

AU - Rosengren, Annika

AU - Wilhelmsen, Lars

AU - Lappas, Georgios

AU - Eriksson, Henry

AU - Björkelund, Cecilia

AU - Lissner, Lauren

AU - Bengtsson, Calle

AU - Cremer, Peter

AU - Nagel, Dorothea

AU - Tilvis, Reijo S.

AU - Strandberg, Timo E.

AU - Rodriguez, Beatriz

AU - Dekker, Jacqueline

AU - Nijpels, G.

AU - Stehouwer, Coen D A

AU - Rimm, Eric

AU - Pai, Jennifer K.

AU - Sato, Shinichi

AU - Iso, Hiroyasu

AU - Kitamura, Akihiko

AU - Noda, Hiroyuki

AU - Salonen, Jukka T.

AU - Nyyssönen, Kristiina

AU - Tuomainen, Tomi Pekka

AU - Deeg, Dorly J H

AU - Poppelaars, Jan L.

AU - Hedblad, Bo

AU - Berglund, Göran

AU - Engström, Gunnar

AU - Verschuren, W. M M

AU - Blokstra, Anneke

AU - Döring, Angela

AU - Koenig, Wolfgang

AU - Meisinger, Christa

AU - Mraz, Wilfried

AU - Bueno-De-Mesquita, H. Bas

AU - Kuller, Lewis H.

AU - Grandits, Greg

AU - Selmer, Randi

AU - Tverdal, Aage

AU - Nystad, Wenche

AU - Gillum, R. F.

AU - Mussolino, Michael

AU - Hankinson, Sue

AU - Manson, Jo Ann E

AU - Cooper, Jackie A.

AU - Bauer, Kenneth A.

AU - Naito, Yoshihiko

AU - Holme, Ingar

AU - Nakagawa, Hideaki

AU - Miura, Katsuyuki

AU - Ducimetiere, Pierre

AU - Jouven, Xavier

AU - Luc, Gérald

AU - Crespo, Carlos J.

AU - Garcia Palmieri, Mario R.

AU - Amouyel, Philippe

AU - Arveiler, Dominique

AU - Evans, Alun

AU - Ferrieres, Jean

AU - Schulte, Helmut

AU - Assmann, Gerd

AU - Shepherd, James

AU - Packard, Chris J.

AU - Sattar, Naveed

AU - Ford, Ian

AU - Cantin, Bernard

AU - Lamarche, Benoît

AU - Després, Jean Pierre

AU - Dagenais, Gilles R.

AU - Barrett-Connor, Elizabeth

AU - Daniels, Lori B.

AU - Laughlin, Gail A.

AU - Gudnason, Vilmundur

AU - Aspelund, Thor

AU - Sigurdsson, Gunnar

AU - Thorsson, Bolli

AU - Trevisan, Maurizio

AU - Witteman, Jacqueline

AU - Kardys, Isabella

AU - Breteler, Monique M B

AU - Hofman, Albert

AU - Tunstall-Pedoe, Hugh

AU - Tavendale, Roger

AU - Lowe, Gordon

AU - Ben-Shlomo, Yoav

AU - Davey-Smith, George

AU - Howard, Barbara V.

AU - Zhang, Ying

AU - Best, Lyle

AU - Umans, Jason

AU - Onat, Altan

AU - Njølstad, Inger

AU - Mathiesen, Ellisiv B.

AU - Løchen, Maja Lisa

AU - Wilsgaard, Tom

AU - Ingelsson, Erik

AU - Sundström, Johan

AU - Lind, Lars

AU - Lannfelt, Lars

AU - Gaziano, J. Michael

AU - Stampfer, Meir

AU - Ridker, Paul M.

AU - Ulmer, Hanno

AU - Diem, Günter

AU - Concin, Hans

AU - Tosetto, Alberto

AU - Rodeghiero, Francesco

AU - Marmot, Michael

AU - Clarke, Robert

AU - Collins, Rory

AU - Fletcher, Astrid

AU - Brunner, Eric

AU - Shipley, Martin

AU - Buring, Julie

AU - Cobbe, Stuart

AU - Robertson, Michele

AU - He, Yao

AU - Ibañez, Alejandro Marin

AU - Feskens, Edith

AU - Kromhout, Daan

AU - Walker, Matthew

AU - Watson, Sarah

AU - Di Angelantonio, Emanuele

AU - Erqou, Sebhat

AU - Kaptoge, Stephen

AU - Lewington, Sarah

AU - Orfei, Lia

AU - Pennells, Lisa

AU - Perry, Philip L.

AU - Ray, Kausik K.

AU - Sarwar, Nadeem

AU - Alexander, Myriam

AU - Thompson, Alexander

AU - Thompson, Simon G.

AU - Wensley, Frances

AU - White, Ian R.

AU - Wood, Angela M.

AU - Danesh, John

PY - 2009/7/22

Y1 - 2009/7/22

N2 - Context Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein–like particle, may be associated with risk of coronary heart disease (CHD) and stroke. Objective To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. Study Selection Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. Data Extraction Individual records were provided for each of 126 634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22 076 firstever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. Data Synthesis Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 personyears and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. Conclusion Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

AB - Context Circulating concentration of lipoprotein(a) (Lp[a]), a large glycoprotein attached to a low-density lipoprotein–like particle, may be associated with risk of coronary heart disease (CHD) and stroke. Objective To assess the relationship of Lp(a) concentration with risk of major vascular and nonvascular outcomes. Study Selection Long-term prospective studies that recorded Lp(a) concentration and subsequent major vascular morbidity and/or cause-specific mortality published between January 1970 and March 2009 were identified through electronic searches of MEDLINE and other databases, manual searches of reference lists, and discussion with collaborators. Data Extraction Individual records were provided for each of 126 634 participants in 36 prospective studies. During 1.3 million person-years of follow-up, 22 076 firstever fatal or nonfatal vascular disease outcomes or nonvascular deaths were recorded, including 9336 CHD outcomes, 1903 ischemic strokes, 338 hemorrhagic strokes, 751 unclassified strokes, 1091 other vascular deaths, 8114 nonvascular deaths, and 242 deaths of unknown cause. Within-study regression analyses were adjusted for within-person variation and combined using meta-analysis. Analyses excluded participants with known preexisting CHD or stroke at baseline. Data Synthesis Lipoprotein(a) concentration was weakly correlated with several conventional vascular risk factors and it was highly consistent within individuals over several years. Associations of Lp(a) with CHD risk were broadly continuous in shape. In the 24 cohort studies, the rates of CHD in the top and bottom thirds of baseline Lp(a) distributions, respectively, were 5.6 (95% confidence interval [CI], 5.4-5.9) per 1000 personyears and 4.4 (95% CI, 4.2-4.6) per 1000 person-years. The risk ratio for CHD, adjusted for age and sex only, was 1.16 (95% CI, 1.11-1.22) per 3.5-fold higher usual Lp(a) concentration (ie, per 1 SD), and it was 1.13 (95% CI, 1.09-1.18) following further adjustment for lipids and other conventional risk factors. The corresponding adjusted risk ratios were 1.10 (95% CI, 1.02-1.18) for ischemic stroke, 1.01 (95% CI, 0.98-1.05) for the aggregate of nonvascular mortality, 1.00 (95% CI, 0.97-1.04) for cancer deaths, and 1.00 (95% CI, 0.95-1.06) for nonvascular deaths other than cancer. Conclusion Under a wide range of circumstances, there are continuous, independent, and modest associations of Lp(a) concentration with risk of CHD and stroke that appear exclusive to vascular outcomes.

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U2 - 10.1001/jama.2009.1063

DO - 10.1001/jama.2009.1063

M3 - Review article

C2 - 19622820

AN - SCOPUS:67651210632

SN - 0098-7484

VL - 302

SP - 412

EP - 423

JO - JAMA

JF - JAMA

IS - 4

ER -

Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality

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