Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study

Authors: LAMON-FAVA, STEFANIA - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; MARCOVINA, SANTICA M. - UNIVERSITY OF WASHINGTON; ALBERS, JOHN J. - UNIVERSITY OF WASHINGTON; KENNEDY, HAL - UNIVERSITY OF WASHINGTON; DELUCA, CARL - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; WHITE, CHARLES C. - BOSTON UNIVERSITY; CUPPLES, L. ADRIENNE - BOSTON UNIVERSITY; MCNAMARA, JUDITH R. - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; SEMAN, LEO J. - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; BONGARD, VANINA - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; SCHAEFER, ERNST J. - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY

Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/23/2011
Publication Date: 4/7/2011
Citation: Lamon-Fava, S., Marcovina, S., Albers, J., Kennedy, H., Deluca, C., White, C., Cupples, L., Mcnamara, J., Seman, L., Bongard, V., Schaefer, E. 2011. Lipoprotein(a) levels, apo(a) isoform size, and coronary heart disease risk in the Framingham Offspring Study. Journal of Lipid Research. 52(6):1181-1187.

Interpretive Summary: Lipoprotein(a), or Lp(a), is a lipoprotein secreted by the liver and circulating in blood. Several studies have previously demonstrated that individuals with elevated levels of Lp(a) in the blood are at increased risk of coronary heart disease (CHD). In the majority of the these studies, values of Lp(a) were assessed when subjects had already developed CHD. In this study, we evaluated the risk of CHD associated with elevated Lp(a) levels in men and women participating in the Framingham Offspring study, a longitudinal study carried out in the population of Framingham (MA). Lp(a) was measured in plasma samples collected between 1991 and 1995 in 1,328 men and 1,562 women who were free of CHD at the time. Subjects were divided in three groups according to their plasma Lp(a) levels. Subjects were followed for an average of 12 years, during which 98 men and 47 women developed CHD. Our analysis indicated that, in men, the group of subjects with the highest Lp(a) levels had a 2.4-fold increase in CHD risk, relative to subjects in the group with the lowest Lp(a) levels. In women, we were not able to detect an association between Lp(a) levels and CHR risk, probably because of the small number of CHD cases. Our data indicate that elevated plasma Lp(a) levels are a significant and independent predictor of CHD risk in men.

Technical Abstract: The aim of this study was to assess the independent contributions of plasma levels of lipoprotein(a) [Lp(a)], Lp(a) cholesterol, and of apo(a) isoform size to prospective coronary heart disease (CHD) risk. Plasma Lp(a) and Lp(a) cholesterol levels, and apo(a) isoform size were measured at examination cycle 5 in subjects participating in the Framingham Offspring Study who were free of CHD. After a mean follow-up of 12.3 years, 98 men and 47 women developed new CHD events. In multivariate analysis, the HR of CHD was approximately two-fold greater in men in the upper tertile of plasma Lp(a) levels, relative to those in the bottom tertile (p less than 0.002). The apo(a) isoform size contributed only modestly to the association between Lp(a) and CHD and was not an independent predictor of CHD. In multivariate analysis, Lp(a) cholesterol was not significantly associated with CHD risk in men. In women, no association between Lp(a) and CHD risk was observed. Elevated plasma Lp(a) levels are a significant and independent predictor of CHD risk in men. The assessment of apo(a) isoform size in this cohort does not add significant information about CHD risk. In addition, the cholesterol content in Lp(a) is not a significant predictor of CHD risk.