Atherosclerosis 153 (2000) 249 – 254 Lipoprotein (a) is associated with endothelial function in healthy postmenopausal women Hanneke W. Wilmink a,b , Miriam J.J. de Kleijn b , Michiel L. Bots b, *, Annette A.A. Bak b , Yvonne T. van der Schouw b , Sylvia Engelen c , Jose Planellas c , Jan-Dirk Banga a , Diederick E. Grobbee b a Diision of Internal Medicine, Uniersity Medical Center Utrecht (UMC), Utrecht, The Netherlands b Julius Center for Patient Oriented Research, D01.335, Utrecht Uniersity Medical Center (UMC), Heidelberglaan 100, 3584 CX Utrecht, The Netherlands c Clinical Deelopment Department, NV Organon, Oss, The Netherlands Received 29 August 1999; received in revised form 23 December 1999; accepted 21 January 2000 Abstract Background. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic cardiovascular disease. The atherogenic potential of Lp(a) may be by impairment of endothelial function. Objecties. We investigated the relation of Lp(a) plasma levels to endothelium dependent and independent dilatation of the brachial artery in healthy postmenopausal women. Methods. One hundred and five healthy postmenopausal women aged 52 – 67 years were included in the study. Endothelial function was assessed non-invasively by measuring percent lumen diameter change in the brachial artery after reactive hyperemia and sublingual nitroglycerine spray. Results. Flow mediated dilatation was inversely related to the plasma log Lp(a) level. Mean change per unit log Lp(a) increase: -2.83% (95% CI: -5.22– -0.43). Elevated Lp(a) ( 239 mg/l) (upper quartile) was associated with an impaired flow mediated vasodilatation (2.4% 1.2) compared to Lp(a) 239 mg/l (5.2% 0.7). Adjustment for other cardiovas- cular risk factors did not change the magnitude of the association. Nitroglycerine-induced vasodilatation was not significantly lower in the high Lp(a) level group, compared to the group with normal levels of Lp(a) ( 239 mg/l) (8.0 1.2 vs 11.4% 0.8). Conclusion. Elevated lipoprotein (a) levels are associated with an impaired endothelial function in healthy postmenopausal women, independent of conventional risk factors for cardiovascular disease. Since Lp(a) may be pathogenetically important for early vascular damage, elevated Lp(a) levels might contribute to the increased cardiovascular risk seen in postmenopausal women. © 2000 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Lipoprotein (a); Endothelial function; Postmenopausal women; Nitric oxide www.elsevier.com/locate/atherosclerosis 1. Introducion Endothelial function is impaired in the presence of known atherogenic risk factors such as hypercholes- terolemia [1,2], hyperlipidemia [3,4], diabetes mellitus [5,6], cigarette smoking [7,8], low plasma estrogen levels [9,10], aging [11] and hypertension [12], even before atherosclerosis becomes clinically manifest. Impaired endothelial function of the brachial artery has also been shown to be present in patients with coronary artery disease [13–15]. These findings led to the view that endothelial dysfunction may be important in the atherosclerotic process and could be of use as an early marker of cardiovascular risk. Lipoprotein (a) (Lp(a)) is an independent risk factor for atherosclerotic vascular disease [16–18]. Many prospective studies have shown that excess Lp(a) is associated with premature coronary atherosclerosis and cardiovascular disease risk, in men and women. In particular in subjects with premature coronary atherosclerosis, therapy to lower Lp(a) deserves atten- tion [19]. To our knowledge no results have been published studying the relation between plasma Lp(a) levels and endothelium dependent dilatation of the * Corresponding author. Tel.: +31-30-2509352; fax: +31-30- 2505485. E-mail address: m.1.bots@jc.azu.n1 (M.L. Bots). 0021-9150/00/$ - see front matter © 2000 Elsevier Science Ireland Ltd. All rights reserved. PII:S0021-9150(00)00411-1