• Emerging Risk Factors Collaboration, Emanuele Di Angelantonio, Pei Gao, Lisa Pennells, Stephen Kaptoge, Muriel Caslake, Alexander Thompson, Adam S Butterworth, Nadeem Sarwar, David Wormser, Danish Saleheen, Christie M Ballantyne, Bruce M Psaty, Johan Sundström, Paul M Ridker, Dorothea Nagel, Richard F Gillum, Ian Ford, Pierre Ducimetiere, Stefan Kiechl, Wolfgang Koenig, Robin P F Dullaart, Gerd Assmann, Ralph B D'Agostino, Gilles R Dagenais, Jackie A Cooper, Daan Kromhout, Altan Onat, Robert W Tipping, Agustín Gómez-de-la-Cámara, Annika Rosengren, Susan E Sutherland, John Gallacher, F Gerry R Fowkes, Edoardo Casiglia, Albert Hofman, Veikko Salomaa, Elizabeth Barrett-Connor, Robert Clarke, Eric Brunner, J Wouter Jukema, Leon A Simons, Manjinder Sandhu, Nicholas J Wareham, Kay-Tee Khaw, Jussi Kauhanen, Jukka T Salonen, William J Howard, Børge G Nordestgaard, Angela M Wood, Simon G Thompson, S Matthijs Boekholdt, Naveed Sattar, Chris Packard, Vilmundur Gudnason, and John Danesh.
• JAMA. 2012 Jun 20; 307 (23): 2499-506.

ContextThe value of assessing various emerging lipid-related markers for prediction of first cardiovascular events is debated.ObjectiveTo determine whether adding information on apolipoprotein B and apolipoprotein A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 to total cholesterol and high-density lipoprotein cholesterol (HDL-C) improves cardiovascular disease (CVD) risk prediction.Design, Setting, And ParticipantsIndividual records were available for 165,544 participants without baseline CVD in 37 prospective cohorts (calendar years of recruitment: 1968-2007) with up to 15,126 incident fatal or nonfatal CVD outcomes (10,132 CHD and 4994 stroke outcomes) during a median follow-up of 10.4 years (interquartile range, 7.6-14 years).Main Outcome MeasuresDiscrimination of CVD outcomes and reclassification of participants across predicted 10-year risk categories of low (<10%), intermediate (10%-<20%), and high (≥20%) risk.ResultsThe addition of information on various lipid-related markers to total cholesterol, HDL-C, and other conventional risk factors yielded improvement in the model's discrimination: C-index change, 0.0006 (95% CI, 0.0002-0.0009) for the combination of apolipoprotein B and A-I; 0.0016 (95% CI, 0.0009-0.0023) for lipoprotein(a); and 0.0018 (95% CI, 0.0010-0.0026) for lipoprotein-associated phospholipase A2 mass. Net reclassification improvements were less than 1% with the addition of each of these markers to risk scores containing conventional risk factors. We estimated that for 100,000 adults aged 40 years or older, 15,436 would be initially classified at intermediate risk using conventional risk factors alone. Additional testing with a combination of apolipoprotein B and A-I would reclassify 1.1%; lipoprotein(a), 4.1%; and lipoprotein-associated phospholipase A2 mass, 2.7% of people to a 20% or higher predicted CVD risk category and, therefore, in need of statin treatment under Adult Treatment Panel III guidelines.ConclusionIn a study of individuals without known CVD, the addition of information on the combination of apolipoprotein B and A-I, lipoprotein(a), or lipoprotein-associated phospholipase A2 mass to risk scores containing total cholesterol and HDL-C led to slight improvement in CVD prediction.

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