@article{3112423,
    title = "Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality",
    author = "Tipping, R.W. and Ford, C.E. and Simpson, L.M. and Walldius, G. and Jungner, I. and Folsom, A.R. and Chambless, L. and Panagiotakos, D. and Pitsavos, C. and Chrysohoou, C. and Stefanadis, C. and Goldbourt, U. and Benderly, M. and Tanne, D. and Whincup, P. and Wannamethee, S.G. and Morris, R.W. and Kiechl, S. and Willeit, J. and Santer, P. and Mayr, A. and Wald, N. and Ebrahim, S. and Lawlor, D. and Yarnell, J. and Gallacher, J. and Casiglia, E. and Tikhonoff, V. and Nietert, P.J. and Sutherland, S.E. and Bachman, D.L. and Cushman, M. and Psaty, B.M. and Tracy, R. and Tybjærg-Hansen, A. and Nordestgaard, B.G. and Frikke-Schmidt, R. and Kamstrup, P.R. and Giampaoli, S. and Palmieri, L. and Panico, S. and Vanuzzo, D. and Pilotto, L. and De La Cámara, A.G. and Gómez Gerique, J.A. and Simons, L. and McCallum, J. and Friedlander, Y. and Fowkes, F.G.R. and Lee, A. and Smith, F.B. and Taylor, J. and Guralnik, J.M. and Phillips, C.L. and Wallace, R.B. and Blazer, D.G. and Brenner, H. and Raum, E. and Müller, H. and Rothenbacher, D. and Jansson, J.-H. and Wennberg, P. and Nissinen, A. and Donfrancesco, C. and Salomaa, V. and Harald, K. and Jousilahti, P. and Vartiainen, E. and Woodward, M. and D’Agostino, R.B. and Wolf, P.A. and Vasan, R.S. and Pencina, M.J. and Bladbjerg, E.-M. and Jørgensen, T. and Møller, L. and Jespersen, J. and Dankner, R. and Chetrit, A. and Lubin, F. and Rosengren, A. and Wilhelmsen, L. and Lappas, G. and Eriksson, H. and Björkelund, C. and Lissner, L. and Bengtsson, C. and Cremer, P. and Nagel, D. and Tilvis, R.S. and Strandberg, T.E. and Rodriguez, B. and Dekker, J. and Nijpels, G. and Stehouwer, C.D.A. and Rimm, E. and Pai, J.K. and Sato, S. and Iso, H. and Kitamura, A. and Noda, H. and Salonen, J.T. and Nyyssönen, K. and Tuomainen, T.-P. and Deeg, D.J.H. and Poppelaars, J.L. and Hedblad, B. and Berglund, G. and Engström, G. and Verschuren, W.M.M. and Blokstra, A. and Döring, A. and Koenig, W. and Meisinger, C. and Mraz, W. and Bueno-De-Mesquita, H.B. and Kuller, L.H. and Grandits, G. and Selmer, R. and Tverdal, A. and Nystad, W. and Gillum, R.F. and Mussolino, M. and Hankinson, S. and Manson, J.E. and Cooper, J.A. and Bauer, K.A. and Naito, Y. and Holme, I. and Nakagawa, H. and Miura, K. and Ducimetiere, P. and Jouven, X. and Luc, G. and Crespo, C.J. and Garcia Palmieri, M.R. and Amouyel, P. and Arveiler, D. and Evans, A. and Ferrieres, J. and Schulte, H. and Assmann, G. and Shepherd, J. and Packard, C.J. and Sattar, N. and Ford, I. and Cantin, B. and Lamarche, B. and Després, J.-P. and Dagenais, G.R. and Barrett-Connor, E. and Daniels, L.B. and Laughlin, G.A. and Gudnason, V. and Aspelund, T. and Sigurdsson, G. and Thorsson, B. and Trevisan, M. and Witteman, J. and Kardys, I. and Breteler, M.M.B. and Hofman, A. and Tunstall-Pedoe, H. and Tavendale, R. and Lowe, G. and Ben-Shlomo, Y. and Davey-Smith, G. and Howard, B.V. and Zhang, Y. and Best, L. and Umans, J. and Onat, A. and Njølstad, I. and Mathiesen, E.B. and Løchen, M.-L. and Wilsgaard, T. and Ingelsson, E. and Sundström, J. and Lind, L. and Lannfelt, L. and Gaziano, J.M. and Stampfer, M. and Ridker, P.M. and Ulmer, H. and Diem, G. and Concin, H. and Tosetto, A. and Rodeghiero, F. and Marmot, M. and Clarke, R. and Collins, R. and Fletcher, A. and Brunner, E. and Shipley, M. and Buring, J. and Cobbe, S. and Robertson, M. and He, Y. and Ibañez, A.M. and Feskens, E. and Kromhout, D. and Walker, M. and Watson, S. and Di Angelantonio, E. and Erqou, S. and Kaptoge, S. and Lewington, S. and Orfei, L. and Pennells, L. and Perry, P.L. and Ray, K.K. and Sarwar, N. and Alexander, M. and Thompson, A. and Thompson, S.G. and Wensley, F. and White, I.R. and Wood, A.M. and Danesh, J.",
    journal = "JAMA - JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION - INTERNATIONAL EDITION",
    year = "2009",
    volume = "302",
    number = "4",
    pages = "412-423",
    publisher = "American Medical Association",
    issn = "0098-7484",
    doi = "10.1001/jama.2009.1063",
    keywords = "lipid;  lipoprotein;  lipoprotein A, age distribution;  angina pectoris;  cancer mortality;  cardiovascular risk;  cerebrovascular accident;  clinical assessment;  cohort analysis;  concentration response;  death;  disease association;  follow up;  heart infarction;  human;  morbidity;  mortality;  outcome assessment;  priority journal;  prospective study;  protein blood level;  review;  sex difference;  stroke;  blood;  cause of death;  coronary artery disease;  meta analysis;  risk factor;  stroke, Cause of Death;  Coronary Disease;  Humans;  Lipoprotein(a);  Risk Factors;  Stroke",
    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. ©2009 American Medical Association. All rights reserved."
}