Author + information
- Received September 15, 2009
- Revision received October 26, 2009
- Accepted October 26, 2009
- Published online May 11, 2010.
- Sebhat Erqou, MD, PhD*,
- Alexander Thompson, PhD*,
- Emanuele Di Angelantonio, MD, PhD*,
- Danish Saleheen, MBBS, MPhil*,
- Stephen Kaptoge, MSc, PhD*,
- Santica Marcovina, PhD, DSc† and
- John Danesh, DPhil*,* ()
- ↵*Reprint requests and correspondence:
Dr. John Danesh, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratories, Cambridge CB1 8RN, United Kingdom
Objectives The purpose of this study was to assess the association of apolipoprotein(a) (apo[a]) isoforms with cardiovascular disease risk.
Background Although circulating lipoprotein(a) (Lp[a]) is likely to be a causal risk factor in coronary heart disease (CHD), the magnitude of this association is modest. Lipoprotein(a) particles with smaller, rather than larger, apo(a) isoforms may be stronger risk factors.
Methods Information was collated from 40 studies published between January 1970 and June 2009 that reported on associations between apo(a) isoforms and risk of CHD or ischemic stroke (involving a total of 11,396 patients and 46,938 controls).
Results Thirty-six studies used broadly comparable phenotyping and analytic methods to assess apo(a) isoform size. These studies yielded a combined relative risk for CHD of 2.08 (95% confidence intervals [CI]: 1.67 to 2.58) for individuals with smaller versus larger apo(a) isoforms (corresponding approximately to 22 or fewer kringle IV type 2 repeats vs. >22 repeats or analogously an apo[a] molecular weight of <640 kDa vs. ≥640 kDa). There was substantial heterogeneity among these studies (I2= 85%, 80% to 89%), which was mainly explained by differences in the laboratory methods and analytic approaches used. In the 6 studies of ischemic stroke that used comparable phenotypic methods, the combined relative risk was 2.14 (1.85 to 2.97). Overall, however, only 3 studies made allowances for Lp(a) concentration.
Conclusions People with smaller apo(a) isoforms have an approximately 2-fold higher risk of CHD or ischemic stroke than those with larger proteins. Further studies are needed to determine whether the impact of smaller apo(a) isoforms is independent from Lp(a) concentration and other risk factors.
Dr. Erqou has been supported by the Gates Cambridge Trust. Drs. Erqou and Thompson have received consultancy payments from GlaxoSmithKline. Drs. Thompson and Di Angelantonio have been supported by UK Medical Research Councildoctoral training grants. Dr. Saleheen has been supported by the Yousef Jameel Foundation. Dr. Danesh has received research funding from the British Heart Foundation, BUPA Foundation, diaDexus, European Union, Evelyn Trust, Fogarty International Center, GlaxoSmithKline, Medical Research Council, Merck Sharp and Dohme, National Heart, Lung and Blood Institute, National Institute of Neurological Disorders and Stroke, Novartis, Roche, UK Biobank, and Wellcome Trust.
- Received September 15, 2009.
- Revision received October 26, 2009.
- Accepted October 26, 2009.
- American College of Cardiology Foundation