Apolipoprotein(a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants.
OBJECTIVE
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. > or =640 kDa). There was substantial heterogeneity among these studies (I(2) = 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.
Erqou
Sebhat
S
Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
Thompson
Alexander
A
Di Angelantonio
Emanuele
E
Saleheen
Danish
D
Kaptoge
Stephen
S
Marcovina
Santica
S
Danesh
John
J
D053241:Apoprotein(a) / Q000378:metabolism*; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D010316:Particle Size; D020033:Protein Isoforms / Q000378:metabolism; D012307:Risk Factors; D014652:Vascular Diseases / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology
D015415:Biomarkers; D020033:Protein Isoforms; D053241:Apoprotein(a)