Lipoprotein(a) and risk of coronary, cerebrovascular, and peripheral artery disease: the EPIC-Norfolk prospective population study.
OBJECTIVE
Although the association between circulating levels of lipoprotein(a) [Lp(a)] and risk of coronary artery disease (CAD) and stroke is well established, its role in risk of peripheral arterial disease (PAD) remains unclear. Here, we examine the association between Lp(a) levels and PAD in a large prospective cohort. To contextualize these findings, we also examined the association between Lp(a) levels and risk of stroke and CAD and studied the role of low-density lipoprotein as an effect modifier of Lp(a)-associated cardiovascular risk.


RESULTS
Lp(a) levels were measured in apparently healthy participants in the European Prospective Investigation of Cancer (EPIC)-Norfolk cohort. Cox regression was used to quantify the association between Lp(a) levels and risk of PAD, stroke, and CAD outcomes. During 212 981 person-years at risk, a total of 2365 CAD, 284 ischemic stroke, and 596 PAD events occurred in 18 720 participants. Lp(a) was associated with PAD and CAD outcomes but not with ischemic stroke (hazard ratio per 2.7-fold increase in Lp(a) of 1.37, 95% CI 1.25-1.50, 1.13, 95% CI 1.04-1.22 and 0.91, 95% CI 0.79-1.03, respectively). Low-density lipoprotein cholesterol levels did not modify these associations.


CONCLUSIONS
Lp(a) levels were associated with future PAD and CAD events. The association between Lp(a) and cardiovascular disease was not modified by low-density lipoprotein cholesterol levels.
Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, United Kingdom.
Deepti
D
Gurdasani
Barbara
B
Sjouke
Sotirios
S
Tsimikas
G Kees
GK
Hovingh
Robert N
RN
Luben
Nicholas W J
NW
Wainwright
Cristina
C
Pomilla
Nicholas J
NJ
Wareham
Kay-Tee
KT
Khaw
S Matthijs
SM
Boekholdt
Manjinder S
MS
Sandhu
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002561:Cerebrovascular Disorders / Q000097:blood / Q000453:epidemiology*; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000453:epidemiology*; D005060:Europe; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000453:epidemiology*; D011446:Prospective Studies; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000453:epidemiology*; D006113:United Kingdom
D015415:Biomarkers; D017270:Lipoprotein(a); D008077:Lipoproteins, LDL