Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: The Physicians' Health Study.
BACKGROUND
The relationship of lipoprotein (a) [Lp(a)] concentrations with risk of coronary heart disease needs clarification, especially for threshold values for increased risk and for possible interactions with LDL-cholesterol concentrations and apolipoprotein (a) [apo(a)] size polymorphism. This study was designed to examine the ability of baseline Lp(a) concentration and apo(a) size to predict future severe angina pectoris in apparently healthy men.


METHODS
Baseline Lp(a) concentration and apo(a) size were determined in 195 men who subsequently developed angina and in 195 men who remained free of cardiovascular disease for 5 years.


RESULTS
Cases had higher median Lp(a) concentrations than did controls (30.6 vs 22.5 nmol/L; P = 0.02). Lp(a) concentration was predictive of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0, 1.8, and 2.6; P for trend = 0.015]. The increased risk was approximately 4-fold (95% confidence interval, 1.4- to 11-fold) among men who had Lp(a) above the 95th percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95% confidence interval, 1.5- to 43-fold). Small apo(a) size isoforms also significantly predicted risk of angina (RR for lowest quintile = 4.1; P for trend = 0.004). When the independent effect of Lp(a) concentration and apo(a) size was assessed by including them in the same multivariate model, only the association between apo(a) size and risk remained significant.


CONCLUSIONS
High Lp(a) predicts risk of angina, and the risk is substantially increased with high concomitant LDL-cholesterol. Small apo(a) size predicts angina with greater strength and independence than Lp(a) concentration.
Rifai
Nader
N
Department of Laboratory Medicine, Children's Hospital and Harvard Medical School, Boston, MA 02115, USA. nader.rifai@tch.harvard.edu
Ma
Jing
J
Sacks
Frank M
FM
Ridker
Paul M
PM
Hernandez
Wendy Jade L
WJ
Stampfer
Meir J
MJ
Marcovina
Santica M
SM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000787:Angina Pectoris / Q000453:epidemiology* / Q000209:etiology; D001053:Apolipoproteins / Q000097:blood* / Q000737:chemistry; D053241:Apoprotein(a); D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000150:complications / Q000453:epidemiology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood* / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D010820:Physicians; D020033:Protein Isoforms / Q000097:blood / Q000737:chemistry; D016032:Randomized Controlled Trials as Topic; D012306:Risk
D001053:Apolipoproteins; D017270:Lipoprotein(a); D020033:Protein Isoforms; D053241:Apoprotein(a)