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http://dx.doi.org/10.3904/kjim.2016.030

Elevated lipoprotein(a) levels predict cardiovascular disease in type 2 diabetes mellitus: a 10-year prospective cohort study  

Lim, Tae-Seok (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Yun, Jae-Seung (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Cha, Seon-Ah (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Song, Ki-Ho (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Yoo, Ki-Dong (Division of Cardiology, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Ahn, Yu-Bae (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Park, Yong-Moon (Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina)
Ko, Seung-Hyun (Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, The Catholic University of Korea)
Publication Information
The Korean journal of internal medicine / v.31, no.6, 2016 , pp. 1110-1119 More about this Journal
Abstract
Background/Aims: Elevated lipoprotein(a) (Lp[a]) level is known to be a risk factor for cardiovascular disease (CVD). However, the data that has been reported on the association between the Lp(a) level and CVD in type 2 diabetes has been limited and incoherent. The aim of this study was to investigate the relationship between the Lp(a) concentration and new onset CVD in type 2 diabetes. Methods: From March 2003 to December 2004, patients with type 2 diabetes without a prior history of CVD were consecutively enrolled. CVD was defined as the occurrence of coronary artery disease or ischemic stroke. Cox proportional hazards models were used to identify the associations between the Lp(a) and CVD after adjusting for confounding variables. Results: Of the 1,183 patients who were enrolled, 833 participants were evaluated with a median follow-up time of 11.1 years. A total of 202 participants were diagnosed with CVD (24.2%). The median Lp(a) level for 1st and 4th quartile group was 5.4 (3.5 to 7.1) and 55.7 mg/dL (43.1 to 75.3). Compared with patients without CVD, those with CVD were older, had a longer duration of diabetes and hypertension, and used more insulin and angiotensin converting enzyme inhibitors/angiotensin receptor blockers at baseline. A Cox hazard regression analysis revealed that the development of CVD was significantly associated with serum Lp(a) level (hazard ratio, 1.92; 95% confidence interval [CI], 1.26 to 2.92; p < 0.001, comparing the 4th vs. 1st quartile of Lp[a]). Conclusions: Elevated Lp(a) level was an independent predictable risk factor for CVD in type 2 diabetes. Other cardiovascular risk factors should be treated more intensively in type 2 diabetic patients with high Lp(a) levels.
Keywords
Lipoprotein(a); Cardiovascular diseases; Diabetes mellitus, type 2;
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1 National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 2002;106:3143-3421.
2 Utermann G. Lipoprotein (a). In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 2001 ed. New York: Mc-Graw-Hill, Medical Publishing Division, 2006:2753-2787.
3 Lamon-Fava S, Diffenderfer MR, Marcovina SM. Lipoprotein(a) metabolism. Curr Opin Lipidol 2014;25:189-193.   DOI
4 Emerging Risk Factors Collaboration, Erqou S, Kaptoge S, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA 2009;302:412-423.   DOI
5 Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA 2009;301:2331-2339.   DOI
6 Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease: meta-analysis of prospective studies. Circulation 2000;102:1082-1085.   DOI
7 Kamstrup PR, Nordestgaard BG. Lipoprotein(a) concentrations, isoform size, and risk of type 2 diabetes: a Mendelian randomisation study. Lancet Diabetes Endocrinol 2013;1:220-227.   DOI
8 Qi Q, Workalemahu T, Zhang C, Hu FB, Qi L. Genetic variants, plasma lipoprotein(a) levels, and risk of cardiovascular morbidity and mortality among two prospective cohorts of type 2 diabetes. Eur Heart J 2012;33:325-334.   DOI
9 Shai I, Schulze MB, Manson JE, Stampfer MJ, Rifai N, Hu FB. A prospective study of lipoprotein(a) and risk of coronary heart disease among women with type 2 diabetes. Diabetologia 2005;48:1469-1476.   DOI
10 Nielsen LB, Gronholdt ML, Schroeder TV, Stender S, Nordestgaard BG. In vivo transfer of lipoprotein(a) into human atherosclerotic carotid arterial intima. Arterioscler Thromb Vasc Biol 1997;17:905-911.   DOI
11 Baldo G, Giunco S, Kontothanassis D, Baiocchi MR, Valerio A, Frego M. Different apoprotein(a) isoform proportions in serum and carotid plaque. Atherosclerosis 2007;193:177-185.   DOI
12 Kamstrup PR. Lipoprotein(a) and ischemic heart disease: a causal association? A review. Atherosclerosis 2010;211:15-23.   DOI
13 Tsimikas S, Bergmark C, Beyer RW, et al. Temporal increases in plasma markers of oxidized low-density lipoprotein strongly reflect the presence of acute coronary syndromes. J Am Coll Cardiol 2003;41:360-370.
14 Kronenberg F. Epidemiology, pathophysiology and therapeutic implications of lipoprotein(a) in kidney disease. Expert Rev Cardiovasc Ther 2004;2:729-743.   DOI
15 Willeit P, Kiechl S, Kronenberg F, et al. Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol 2014;64:851-860.   DOI
16 Kostner KM, Marz W, Kostner GM. When should we measure lipoprotein (a)? Eur Heart J 2013;34:3268-3276.   DOI
17 Ginier P, Deedwania P. Lipoprotein(a) in patients who have non-insulin-dependent diabetes with and without coronary artery disease. Endocr Pract 1997;3:276-280.   DOI
18 Hernandez C, Francisco G, Chacon P, Simo R. Lipoprotein(a) as a risk factor for cardiovascular mortality in type 2 diabetic patients: a 10-year follow-up study. Diabetes Care 2005;28:931-933.   DOI
19 Murase T, Okubo M, Amemiya-Kudo M, Ebara T, Mori Y. Impact of elevated serum lipoprotein (a) concentrations on the risk of coronary heart disease in patients with type 2 diabetes mellitus. Metabolism 2008;57:791-795.   DOI
20 Hiraga T, Kobayashi T, Okubo M, et al. Prospective study of lipoprotein(a) as a risk factor for atherosclerotic cardiovascular disease in patients with diabetes. Diabetes Care 1995;18:241-244.   DOI
21 Kang HM, Lee YJ, Kim DJ. The association of self-reported coronary heart disease with diabetes duration in Korea. Diabetes Metab J 2012;36:350-356.   DOI
22 Kwon SW, Lee BK, Hong BK, et al. Prognostic significance of elevated lipoprotein(a) in coronary artery revascularization patients. Int J Cardiol 2013;167:1990-1994.   DOI
23 Ko SH, Kwon HS, Kim DJ, et al. Higher prevalence and awareness, but lower control rate of hypertension in patients with diabetes than general population: the fifth Korean National Health and Nutrition Examination Survey in 2011. Diabetes Metab J 2014;38:51-57.   DOI
24 Levey AS, Stevens LA, Schmid CH, et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009;150:604-612.   DOI
25 Kronenberg F, Lingenhel A, Lhotta K, et al. Lipoprotein(a)- and low-density lipoprotein-derived cholesterol in nephrotic syndrome: impact on lipid-lowering therapy? Kidney Int 2004;66:348-354.   DOI
26 Nordestgaard BG, Chapman MJ, Ray K, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J 2010;31:2844-2853.   DOI
27 Stevens RJ, Kothari V, Adler AI, Stratton IM; United Kingdom Prospective Diabetes Study (UKPDS) Group. The UKPDS risk engine: a model for the risk of coronary heart disease in type II diabetes (UKPDS 56). Clin Sci (Lond) 2001;101:671-679.   DOI
28 Uusitupa MI, Niskanen LK, Siitonen O, Voutilainen E, Pyorala K. Ten-year cardiovascular mortality in relation to risk factors and abnormalities in lipoprotein composition in type 2 (non-insulin-dependent) diabetic and non-diabetic subjects. Diabetologia 1993;36:1175-1184.   DOI
29 Almdal T, Scharling H, Jensen JS, Vestergaard H. The independent effect of type 2 diabetes mellitus on ischemic heart disease, stroke, and death: a population-based study of 13,000 men and women with 20 years of follow-up. Arch Intern Med 2004;164:1422-1426.   DOI
30 Rhee SY, Chon S, Kwon MK, et al. Prevalence of chronic complications in Korean patients with type 2 diabetes mellitus based on the Korean national diabetes program. Diabetes Metab J 2011;35:504-512.   DOI
31 Brown SA, Hutchinson R, Morrisett J, et al. Plasma lipid, lipoprotein cholesterol, and apoprotein distributions in selected US communities: the Atherosclerosis Risk in Communities (ARIC) Study. Arterioscler Thromb 1993;13:1139-1158.   DOI
32 Kostner GM, Avogaro P, Cazzolato G, Marth E, Bittolo-Bon G, Qunici GB. Lipoprotein Lp(a) and the risk for myocardial infarction. Atherosclerosis 1981;38:51-61.   DOI
33 Guan W, Cao J, Steffen BT, et al. Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 2015;35:996-1001.   DOI
34 Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol 2013;61:1146-1156.   DOI
35 Guyton JR, Dahlen GH, Patsch W, Kautz JA, Gotto AM Jr. Relationship of plasma lipoprotein Lp(a) levels to race and to apolipoprotein B. Arteriosclerosis 1985;5:265-272.   DOI
36 Sandholzer C, Hallman DM, Saha N, et al. Effects of the apolipoprotein(a) size polymorphism on the lipoprotein(a) concentration in 7 ethnic groups. Hum Genet 1991;86:607-614.
37 Jenner JL, Ordovas JM, Lamon-Fava S, et al. Effects of age, sex, and menopausal status on plasma lipoprotein(a) levels: the Framingham Offspring Study. Circulation 1993;87:1135-1141.   DOI
38 Marcovina SM, Albers JJ, Jacobs DR Jr, et al. Lipoprotein[a] concentrations and apolipoprotein[a] phenotypes in Caucasians and African Americans: the CARDIA study. Arterioscler Thromb 1993;13:1037-1045.   DOI
39 Chien KL, Lee YT, Sung FC, Su TC, Hsu HC, Lin RS. Lipoprotein (a) level in the population in Taiwan: relationship to sociodemographic and atherosclerotic risk factors. Atherosclerosis 1999;143:267-273.   DOI