Abstract
While oxidized lipoprotein(a) (oxLp(a)) has been indicated to be involved in atherogenesis more than native lipoprotein(a) (Lp(a)), there is still a need to elucidate the associations among oxLp(a), hypertension, and atherosclerosis. The cardio-ankle vascular index (CAVI) is a recently developed index used to assess arterial stiffness that is independent of blood pressure components. The present study investigated the correlation between oxLp(a) and the CAVI among hypertensive subjects. Clinical data, including general atherosclerotic risk factors, in addition to Lp(a), oxLp(a), and the CAVI, were collected from 72 non-smoking, asymptomatic, and untreated female subjects (mean age: 64.3 years). Correlations between the CAVI and Lp(a) or oxLp(a) were examined in a hypertensive group (n = 34) and a non-hypertensive control group (n = 38). There was a significant and positive correlation between the CAVI and subject age in the control group, while there was a significant and positive correlation between the CAVI and subject age, systolic blood pressure, and oxLp(a) (r = 0.38, p < 0.05) in the hypertensive group. A stepwise multiple linear regression analysis identified the oxLp(a) to be correlated independently, significantly, and positively with the CAVI (β = 0.30, p < 0.05) in the hypertensive group, while this correlation was not significant in the control group. These findings suggest that the oxidative modification of Lp(a) may be associated with arterial stiffness in hypertensive, but not non-hypertensive, female subjects.
Similar content being viewed by others
References
Scanu AM (2003) Lipoprotein(a) and the atherothrombotic process: mechanistic insights and clinical implications. Curr Atheroscler Rep 5:106–113
Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J (2009) Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 302:412–423
Nordestgaard BG, Chapman MJ, Ray K, Borén J, Andreotti F, Watts GF, Ginsberg H, Amarenco P, Catapano A, Descamps OS, Fisher E, Kovanen PT, Kuivenhoven JA, Lesnik P, Masana L, Reiner Z, Taskinen MR, Tokgözoglu L, Tybjærg-Hansen A; European Atherosclerosis Society Consensus Panel (2010) Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 31:2844–2853
Holvet P (2004) Oxidized LDL and coronary heart disease. Acta Cardiol 59:279–484
Zioncheck TF, Powell LM, Rice GC, Eaton DL, Lawn RM (1991) Interaction of recombinant apolipoprotein(a) and lipoprotein(a) with macrophages. J Clin Invest 87:767–771
Haberland ME, Fless GM, Scanu AM, Fogelman AM (1992) Malondialdehyde modification of lipoprotein(a) produces avid uptake by human monocyte–macrophages. J Biol Chem 267:4143–4151
Riis-Hansen P, Kharazmi A, Jauhiainen M, Ehnholm C (1994) Induction of oxygen free radical generation in human monocytes by lipoprotein(a). Eur J Clin Invest 24:497–499
Galle J, Bengen J, Schollmeyer P, Wanner C (1995) Impairment of endothelium-dependent dilation in rabbit renal arteries by oxidized lipoprotein(a). Circulation 92:1582 –1589
Beaudeux JL, Césarini ML, Gardès-Albert M, Maclouf J, Merval R, Esposito B, Peynet J, Tedqui A (1997) Native and gamma radiolysis-oxidized lipoprotein(a) increase the adhesiveness of rabbit aortic endothelium. Atherosclerosis 132:29–35
Ren S, Man RY, Angel A, Shen GX (1997) Oxidative modification enhances lipoprotein(a)-induced overproduction of plasminogen activator inhibitor-1 in cultured vascular endothelial cells. Atherosclerosis 128:1–10
Morishita R, Yamada S, Higaki J, Tomita N, Kida I, Aoki M, Moriguchi A, Hayashi S, Sakurabayashi I, Kaneda Y, Ogihara T (1998) Conditioned medium from HepG2 cells transfected with human apolipoprotein(a) gene stimulates growth of human vascular smooth muscle cells: effects of overexpression of human apolipoprotein(a) gene. Hypertension 32:215–222
Yamada S, Morishita R, Nakamura S, Ogihara T, Kusumi Y, Sakurai I, Kubo N, Sakurabayashi I (2000) Development of antibody against epitope of lipoprotein(a) modified by oxidation: evaluation of new enzyme-linked immunosorbent assay for oxidized lipoprotein(a). Circulation 102:1639–1644
Komai N, Morishita R, Yamada S, Oishi M, Iguchi S, Aoki M, Sasaki M, Sakurabayashi I, Higaki J, Ogihara T (2002) Mitogenic activity of oxidized lipoprotein (a) on human vascular smooth muscle cells. Hypertension 40:310–314
Morishita R, Ishii J, Kusumi Y, Yamada S, Komai N, Ohishi M, Nomura M, Hishida H, Niihashi M, Mitsumata M (2009) Association of serum oxidized lipoprotein(a) concentration with coronary artery disease: potential role of oxidized lipoprotein(a) in the vascular wall. J Atheroscler Thromb 16:410–418
Umahara T, Uchihara T, Yamada S, Hashimoto T, Akimoto J, Haraoka J, Iwamoto T (2011) Differential expression of oxidized/native lipoprotein(a) and plasminogen in human carotid and cerebral artery plaques. Atherosclerosis 215:392–398
Kotani K, Yamada S, Uurtuya S, Yamada T, Taniguchi N, Sakurabayashi I (2010) The association between blood glucose and oxidized lipoprotein(a) in healthy young women. Lipids Health Dis 9:103
Kotani K, Yamada S, Yamada T, Taniguchi N, Sakurabayashi I (2011) The relationship between oxidized lipoprotein(a) and carotid atherosclerosis in asymptomatic subjects: a comparison with native lipoprotein(a). Lipids Health Dis 10:174
Rodrigo R, González J, Paoletto F (2011) The role of oxidative stress in the pathophysiology of hypertension. Hypertens Res 34:431–440
Asmar R, Benetos A, Topouchian J, Laurent P, Pannier B, Brisac AM, Target R, Levy BI (1995) Assessment of arterial distensibility by automatic pulse wave velocity measurement. Validation and clinical application studies. Hypertension 26:485–490
Lehmann ED (1999) Clinical value of aortic pulse-wave velocity measurement. Lancet 354:528–529
Mattace-Raso FU, van der Cammen TJ, Hofman A, van Popele NM, Bos ML, Schalekamp MA, Asmar R, Reneman RS, Hoeks AP, Breteler MM, Witteman JC (2006) Arterial stiffness and risk of coronary heart disease and stroke: the Rotterdam Study. Circulation 113:657–663
Willum-Hansen T, Staessen JA, Torp-Pedersen C, Rasmussen S, Thijs L, Ibsen H, Jeppesen J (2006) Prognostic value of aortic pulse wave velocity as index of arterial stiffness in the general population. Circulation 113:664–670
Yamashina A, Tomiyama H, Arai T, Koji Y, Yambe M, Motobe H, Glunizia Z, Yamamoto Y, Hori S (2003) Nomogram of the relation of brachial-ankle pulse wave velocity with blood pressure. Hypertens Res 26:801–806
Shirai K, Utino J, Otsuka K, Takata M (2006) A novel blood pressure-independent arterial wall stiffness parameter; cardio-ankle vascular index (CAVI). J Atheroscler Thromb 13:101–107
Kotani K, Miyamoto M, Taniguchi N (2010) Clinical significance of the cardio-ankle vascular index (CAVI) in hypertension. Curr Hypertens Rev 6:251–253
Shirai K, Hiruta N, Song M, Kurosu T, Suzuki J, Tomaru T, Miyashita Y, Saiki A, Takahashi M, Suzuki K, Takata M (2011) Cardio-ankle vascular index (CAVI) as a novel indicator of arterial stiffness: theory, evidence and perspectives. J Atheroscler Thromb 18:924–938
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ; Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. National Heart, Lung, and Blood Institute; National High Blood Pressure Education Program Coordinating Committee (2003) Seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Hypertension 42:1206–1252
Yamada S, Inoue K, Morishita R, Ogihara T, Kubono K, Kubo N, Abe A, Sakurabayashi I (1999) A new Lp(a) assay that is unaffected by apo(a) size polymorphism. Clin Chim Acta 287:29–43
Homma Y (2004) Predictors of atherosclerosis. J Atheroscler Thromb 11:265–270
Evans M (2011) Total lipid management and residual risk: beyond statin therapy. Br J Hosp Med (Lond) 72:132–136
Taguchi M, Ishigami M, Nishida M, Moriyama T, Yamashita S, Yamamura T (2011) Remnant lipoprotein-cholesterol is a predictive biomarker for large artery atherosclerosis in apparently healthy women: usefulness as a parameter for annual health examinations. Ann Clin Biochem 48:332–337
Taleb A, Witztum JL, Tsimikas S (2012) Oxidized phospholipids on apoB-100-containing lipoproteins: a biomarker predicting cardiovascular disease and cardiovascular events. Biomark Med 5:673–694
Bhavani AB, Padma T, Sastry KB, Reddy NK (2003) Plasma lipoprotein(a) levels in patients with untreated essential hypertension. Indian J Hum Genet 9:65–68
Serban C, Nicola T, Mateescu R, Noveanu L, Susan L, Pacurari A, Caraba A, Romoşan I, Cristescu A (2010) Serum lipoprotein (a) levels in patients with arterial hypertension. Rev Med Chir Soc Med Nat Iasi 114:798–802
Nagayama D, Saiki A, Endo K, Yamaguchi T, Ban N, Kawana H, Ohira M, Oyama T, Miyashita Y, Shirai K (2010) Improvement of cardio-ankle vascular index by glimepiride in type 2 diabetic patients. Int J Clin Pract 64:1796–1801
Miyashita Y, Saiki A, Endo K, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K (2009) Effects of olmesartan, an angiotensin II receptor blocker, and amlodipine, a calcium channel blocker, on Cardio-Ankle Vascular Index (CAVI) in type 2 diabetic patients with hypertension. J Atheroscler Thromb 16:621–626
Miyashita Y, Endo K, Saiki A, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohira M, Oyama T, Shirai K (2009) Effects of pitavastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on cardio-ankle vascular index in type 2 diabetic patients. J Atheroscler Thromb 16:539–545
Sasaki H, Saiki A, Endo K, Ban N, Yamaguchi T, Kawana H, Nagayama D, Ohhira M, Oyama T, Miyashita Y, Shirai K (2009) Protective effects of efonidipine, a T- and L-type calcium channel blocker, on renal function and arterial stiffness in type 2 diabetic patients with hypertension and nephropathy. J Atheroscler Thromb 16:568–575
Ishimitsu T, Numabe A, Masuda T, Akabane T, Okamura A, Minami J, Matsuoka H (2009) Angiotensin-II receptor antagonist combined with calcium channel blocker or diuretic for essential hypertension. Hypertens Res 32:962–968
Madamanchi NR, Hakim ZS, Runge MS (2005) Oxidative stress in atherogenesis and arterial thrombosis: the disconnect between cellular studies and clinical outcomes. J Thromb Haemos 3:254–267
Tavridou A, Efthimiadis A, Efthimiadis I, Manolopoulos VG (2010) Simvastatin-induced changes in circulating oxidized low-density lipoprotein in different types of dyslipidemia. Heart Vessels 25:288–293
Miyoshi T, Doi M, Hirohata S, Kamikawa S, Usui S, Ogawa H, Sakane K, Izumi R, Ninomiya Y, Kusachi S (2011) Olmesartan reduces arterial stiffness and serum adipocyte fatty acid-binding protein in hypertensive patients. Heart Vessels 26:408–413
Chien KL, Lee YT, Sung FC, Su TC, Hsu HC, Lin RS (1999) Lipoprotein (a) level in the population in Taiwan: relationship to sociodemographic and atherosclerotic risk factors. Atherosclerosis 143:267–273
No authors listed (1991) Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of Systolic Hypertension in the Elderly (SHEP). SHEP cooperative research group. JAMA 265:3255–3264
Acknowledgments
This study was supported in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (K.K) and the Foundation for the Development of the Community, Japan.
Conflict of interest
The authors have no conflicts of interest to report. The authors alone are responsible for the content and writing of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kotani, K., Yamada, S., Yamada, T. et al. Oxidized lipoprotein(a) and cardio-ankle vascular index (CAVI) in hypertensive subjects. Heart Vessels 28, 461–466 (2013). https://doi.org/10.1007/s00380-012-0265-2
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00380-012-0265-2