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 |
|---|---|
| Journal | JAMA |
| Volume | 302 |
| Issue number | 4 |
| Pages (from-to) | 412-423 |
| Number of pages | 12 |
| ISSN | 0098-7484 |
| DOIs | |
| Publication status | Published - 22 Jul 2009 |
Bibliographical note
Publisher Copyright:©2009 American Medical Association. All rights reserved.
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Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. / Tipping, Robert W.; Ford, Charles E.; Simpson, Lara M.; Walldius, Göran; Jungner, Ingmar; Folsom, Aaron R.; Chambless, Lloyd; Panagiotakos, Demosthenes; Pitsavos, Christos; Chrysohoou, Christina; Stefanadis, Christodoulos; Goldbourt, Uri; Benderly, Michal; Tanne, David; Whincup, Peter; Wannamethee, S. Goya; Morris, Richard W.; Kiechl, Stefan; Willeit, Johann; Santer, Peter; Mayr, Agnes; Wald, Nicholas; Ebrahim, Shah; Lawlor, Debbie; Yarnell, John; Gallacher, John; Casiglia, Edoardo; Tikhonoff, Valérie; Nietert, Paul J.; Sutherland, Susan E.; Bachman, David L.; Cushman, Mary; Psaty, Bruce M.; Tracy, Russ; Tybjærg-Hansen, Anne; Nordestgaard, Børge G.; Frikke-Schmidt, Ruth; Kamstrup, Pia R.; Giampaoli, Simona; Palmieri, Luigi; Panico, Salvatore; Vanuzzo, Diego; Pilotto, Lorenza; De La Cámara, Agustín Gómez; Gómez Gerique, Juan A.; Simons, Leon; McCallum, John; Friedlander, Yechiel; Fowkes, F. Gerry R.; Lee, Amanda; Smith, Felicity B.; Taylor, James; Guralnik, Jack M.; Phillips, Caroline L.; Wallace, Robert B.; Blazer, Dan G.; Brenner, Hermann; Raum, Elke; Müller, Heiko; Rothenbacher, Dietrich; Jansson, Jan Håkan; Wennberg, Patrik; Nissinen, Aulikki; Donfrancesco, Chiara; Salomaa, Veikko; Harald, Kennet; Jousilahti, Pekka; Vartiainen, Erkki; Woodward, Mark; D’Agostino, Ralph B.; Wolf, Philip A.; Vasan, Ramachandran S.; Pencina, Michael J.; Bladbjerg, Else Marie; Jørgensen, Torben; Møller, Lars; Jespersen, Jørgen; Dankner, Rachel; Chetrit, Angela; Lubin, Flora; Rosengren, Annika; Wilhelmsen, Lars; Lappas, Georgios; Eriksson, Henry; Björkelund, Cecilia; Lissner, Lauren; Bengtsson, Calle; Cremer, Peter; Nagel, Dorothea; Tilvis, Reijo S.; Strandberg, Timo E.; Rodriguez, Beatriz; Dekker, Jacqueline; Nijpels, G.; Stehouwer, Coen D.A.; Rimm, Eric; Pai, Jennifer K.; Sato, Shinichi; Iso, Hiroyasu; Kitamura, Akihiko; Noda, Hiroyuki; Salonen, Jukka T.; Nyyssönen, Kristiina; Tuomainen, Tomi Pekka; Deeg, Dorly J.H.; Poppelaars, Jan L.; Hedblad, Bo; Berglund, Göran; Engström, Gunnar; Verschuren, W. M.M.; Blokstra, Anneke; Döring, Angela; Koenig, Wolfgang; Meisinger, Christa; Mraz, Wilfried; Bueno-De-Mesquita, H. Bas; Kuller, Lewis H.; Grandits, Greg; Selmer, Randi; Tverdal, Aage; Nystad, Wenche; Gillum, R. F.; Mussolino, Michael; Hankinson, Sue; Manson, Jo Ann E.; Cooper, Jackie A.; Bauer, Kenneth A.; Naito, Yoshihiko; Holme, Ingar; Nakagawa, Hideaki; Miura, Katsuyuki; Ducimetiere, Pierre; Jouven, Xavier; Luc, Gérald; Crespo, Carlos J.; Garcia Palmieri, Mario R.; Amouyel, Philippe; Arveiler, Dominique; Evans, Alun; Ferrieres, Jean; Schulte, Helmut; Assmann, Gerd; Shepherd, James; Packard, Chris J.; Sattar, Naveed; Ford, Ian; Cantin, Bernard; Lamarche, Benoît; Després, Jean Pierre; Dagenais, Gilles R.; Barrett-Connor, Elizabeth; Daniels, Lori B.; Laughlin, Gail A.; Gudnason, Vilmundur; Aspelund, Thor; Sigurdsson, Gunnar; Thorsson, Bolli; Trevisan, Maurizio; Witteman, Jacqueline; Kardys, Isabella; Breteler, Monique M.B.; Hofman, Albert; Tunstall-Pedoe, Hugh; Tavendale, Roger; Lowe, Gordon; Ben-Shlomo, Yoav; Davey-Smith, George; Howard, Barbara V.; Zhang, Ying; Best, Lyle; Umans, Jason; Onat, Altan; Njølstad, Inger; Mathiesen, Ellisiv B.; Løchen, Maja Lisa; Wilsgaard, Tom; Ingelsson, Erik; Sundström, Johan; Lind, Lars; Lannfelt, Lars; Gaziano, J. Michael; Stampfer, Meir; Ridker, Paul M.; Ulmer, Hanno; Diem, Günter; Concin, Hans; Tosetto, Alberto; Rodeghiero, Francesco; Marmot, Michael; Clarke, Robert; Collins, Rory; Fletcher, Astrid; Brunner, Eric; Shipley, Martin; Buring, Julie; Cobbe, Stuart; Robertson, Michele; He, Yao; Ibañez, Alejandro Marin; Feskens, Edith; Kromhout, Daan; Walker, Matthew; Watson, Sarah; Di Angelantonio, Emanuele; Erqou, Sebhat; Kaptoge, Stephen; Lewington, Sarah; Orfei, Lia; Pennells, Lisa; Perry, Philip L.; Ray, Kausik K.; Sarwar, Nadeem; Alexander, Myriam; Thompson, Alexander; Thompson, Simon G.; Wensley, Frances; White, Ian R.; Wood, Angela M.; Danesh, John.
In: JAMA, Vol. 302, No. 4, 22.07.2009, p. 412-423.Research output: Contribution to journal › Review › Research › peer-review
}
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
N1 - Publisher Copyright: ©2009 American Medical Association. All rights reserved.
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.
UR - http://www.scopus.com/inward/record.url?scp=67651210632&partnerID=8YFLogxK
U2 - 10.1001/jama.2009.1063
DO - 10.1001/jama.2009.1063
M3 - Review
C2 - 19622820
AN - SCOPUS:67651210632
VL - 302
SP - 412
EP - 423
JO - JAMA - Journal of the American Medical Association
JF - JAMA - Journal of the American Medical Association
SN - 0098-7484
IS - 4
ER -