A 113

Details of study selection, data collection, and harmonization procedures in the Emerging Risk Factors Collaboration (ERFC) have been described previously.^{19 (link)} Studies were identified through electronic searches of databases, scanning of the reference lists of relevant articles (including previously published reviews), and discussion with collaborators of the ERFC (FIGURE 1). Electronic searches, not limited to the English language, were performed in MEDLINE and EMBASE for studies published between January 1970 and March 2009 using terms related to Lp(a) (eg, lipoprotein[a], Lp[a], apo[a], apolipoprotein[a]) and cardiovascular disease outcomes (eg, cardiovascular disease, coronary heart disease, myocardial infarction, stroke).
Studies were considered for inclusion if they had baseline information on age, sex, Lp(a), and several conventional vascular risk factors; if they did not select participants on the basis of having previous cardiovascular disease; used quantitative Lp(a) assay methods; recorded cause-specific mortality and/or major vascular morbidity using accepted criteria; and had accrued more than 1 year of follow-up.
Thirty-six eligible prospective studies,^{10 (link),15 (link),16 (link),20 (link)-52 (link)} including 12 that had not previously published their findings (references 21 (link), 24 (link), 29 (link), 31 (link), 32 (link), 38 (link)-42 (link), 47 (link), 50 (link)), were included. These studies involved a total of 126 634 individuals who had no known prior history of CHD (ie, myocardial infarction [MI] or angina, which was defined in each study) or stroke at the initial (baseline) examination. The contributing studies comprise about 90% of relevant incident CHD cases identified in known Western studies (TABLE 1); several smaller studies (collectively comprising about 10% of relevant known incident CHD cases) could not supply data.^{53 (link)-61 (link)} A few studies^{62 (link)-64 (link)} could not be included because they did not use quantitative assay methods.
Concomitant information was available on Lp(a), age, sex, systolic blood pressure, smoking habits, history of diabetes, body mass index, triglycerides, and total cholesterol in 106 645 participants from 30 studies. A total of 96 113 participants from 26 studies had concomitant data on all the preceding characteristics plus high-density lipoprotein (HDL) cholesterol. To measure Lp(a), 2 studies used in-house assays, 32 used commercially available assays, and 2 did not specify the assay used. Twenty-one studies used enzyme-linked immunosorbent assay methods, 9 immunoturbimetry or nephelometry, 3 immunoradiometry, and 1enzyme immunodiffusion (eTable 1; available at http://www.jama.com). Twenty-four studies used assays insensitive to apo(a) isoforms.
In registering fatal outcomes, all contributing studies used International Classification of Diseases coding to at least 3 digits and ascertainment was based on death certificates. Twenty-eight of the 36 contributing studies also involved medical records, autopsy findings, and other supplementary sources to help classify deaths (eTable 2). Twenty-nine studies used standard definitions of MI based on Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) or World Health Organization criteria. Twenty-five studies reported diagnosis of strokes on the basis of typical clinical features and characteristic changes on brain imaging, and most attempted to provide attribution of stroke subtype.