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 journalReview articlepeer-review

889 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 languageEnglish (US)
Pages (from-to)412-423
Number of pages12
JournalJAMA - Journal of the American Medical Association
Volume302
Issue number4
DOIs
StatePublished - Jul 22 2009

Bibliographical note

Publisher Copyright:
©2009 American Medical Association. All rights reserved.

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