Small-dense low density lipoprotein (sdLDL) is increasingly viewed as a marker for evaluating atherogenic risk, however its clinical uptake is hampered by the cumbersomeness of available methods. Consequently, a number of alternative methods for the estimation of sdLDL have been developed and none have been tested in a population from Africa. We evaluated an equation to estimate sdLDL-C from classic lipid parameters in South Africans. This is a cross-sectional study involving 1550 participants in which direct measurement of sdLDL in 237 participants was performed using a homogeneous enzymatic assay. Their mean age (standard deviation, SD) was 54.2 (14.7) years. 156 (65.8%) were normotolerant, 29 (12.2%) prediabetes, 17 (7.2%) screen detected diabetes and 35 (14.8%) known diabetes. Measured sdLDL values ranged from 0.17 to 3.39 versus—1.85 to 2.52 mmol/L calculated sdLDL. There was a significant positive correlation between the two measurements with a Pearson correlation coefficient of 0.659 (95%CI: 0.581–0.726). In a regression model, the adjusted R2 was 0.440 after adding age, 0.441 after further adding gender, then 0.443 with dysglycemia and lastly 0.447 upon adding body mass index. With the exception of HDL-cholesterol levels that decreased across increasing quintiles of calculated sdLDL, our data showed significant correlations between sdLDL and cardiometabolic risk factors, all p values < 0.0001. In conclusion, this study has shown that calculated sdLDL can be efficiently used to approximate population levels of sdLDL; however the modest correlation indicate that at the individual level, it will poorly approximate true sdLDL levels, with possible implications for risk stratification.
Africa Diabetes Metabolic syndrome Lipids Small-dense low density lipoprotein
This is a preview of subscription content, log in to check access.
We thank the Bellville South (Ward 009) community for participating in the study. We are also grateful to the Bellville South community Health Forum for supporting the engagement with the Bellville South community. This research project was funded by the South African Medical Research Council (SAMRC) with funds from National Treasury under its Economic Competitiveness and Support Package (MRC-RFA-UFSP-01-2013/VMH Study) and strategic funds from the SAMRC received from the South African National Department of Health. Any opinion, finding and conclusion or recommendation expressed in this material is that of the author(s) and the MRC does not accept any liability in this regard.
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; 106:3143–421.Google Scholar
Krauss RM, Blanche PJ. Detection and quantitation of LDL subfractions. Curr Opin Lipidol. 1992;3:373–83.CrossRefGoogle Scholar
Krauss RM. Heterogeneity of plasma low-density lipoproteins and atherosclerosis risk. Curr Opin Lipidol. 1994;5:339–49.CrossRefPubMedGoogle Scholar
De Graaf J, Hak-Lemmers HL, Hectors MP, Demacker PN, Hendriks JC, Stalenhoef AF. Enhanced susceptibility to in vitro oxidation of the dense low-density lipoprotein subfraction in healthy subjects. Arterioscler Thromb Vasc Biol. 1991;11:298–306.CrossRefGoogle Scholar
Ito Y, Fujimura M, Ohta M, Hirano T. Development of a homogeneous assay for measurement of small dense LDL cholesterol. Clin Chem. 2011;57:57–65.CrossRefPubMedGoogle Scholar
Srisawasdi P, Chaloeysup S, Teerajetgul Y, Pocathikorn A, Sukasem C, Vanavanan S, et al. Estimation of plasma small dense LDL cholesterol from classic lipid measures. Am J Clin Pathol. 2011;136:20–9.CrossRefPubMedGoogle Scholar
Cho Y, Kim Y, Kim JH, Jee SH, Han K. The plasma small dense LDL-cholesterol calculation formula proposed by Srisawasdi et al is not applicable to Koreans who are healthy or have metabolic syndrome. Am J Clin Pathol. 2012;138:754–5.CrossRefPubMedGoogle Scholar
Erasmus RT, Soita DJ, Hassan MS, Blanco Blanco E, Vergotine Z, Kengne AP, et al. High prevalence of diabetes mellitus and metabolic syndrome in a South African coloured population: baseline data of a study in Bellville, Cape Town. S Afr Med J. 2012;102:841–4.CrossRefPubMedGoogle Scholar
Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L, et al. 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clin Exp Hypertens. 1999;21:1009–60.CrossRefPubMedGoogle Scholar
World Health Organization (WHO). 2016. Global Report on Diabetes. Recommendations for the Diagnostic Criteria for Diabetes and Intermediate Hyperglycaemia. http://www.who.int, WHO Press, World Health Organization, 20 Avenue Appia, 1211 Geneva 27, Switzerland.
Anscombe FG, Glynn WJ. Distribution of kurtosis statistic for normal statistics. Biometrika. 1983;70:227–34.Google Scholar
D’Agostino RB Sr. Transformation to normality of the null distribution of g1. Biometrika. 1970;57:679–81.Google Scholar
Bland Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet. 1986;1:307–10.CrossRefPubMedGoogle Scholar
Lara-Riegos J, Brambila E, Ake-Ku A, Villegas-Hernandez V, Quintero-Carrilo C, Ortiz-Andrade R, et al. Short-term estimation and application of biological variation of small dense low-density lipoproteins in healthy individuals. Clin Chem Lab Med. 2013;51:2167–72.CrossRefPubMedGoogle Scholar
Nikolic D, Katsiki N, Montalto G, Isenovic ER, Mikhailidis DP, Rizzo M. Lipoprotein subfractions in metabolic syndrome and obesity: clinical significance and therapeutic approaches. Nutrients. 2013;5:928–48.CrossRefPubMedPubMedCentralGoogle Scholar
Hattori Y, Suzuki M, Tsushima M, Yoshida M, Tokunaga Y, Wang Y, et al. Development of approximate formula for LDL-chol, LDL-apo B and LDL-chol/LDL-apo B as indices of hyperapobetalipoproteinemia and small dense LDL. Atherosclerosis. 1998;138:289–99.CrossRefPubMedGoogle Scholar
Wägner AM, Jorba O, Rigla M, Alonso E, Ordonez-Llanos J, Pérez A. LDL-cholesterol/apolipoprotein B ratio is a good predictor of LDL phenotype B in type 2 diabetes. Acta Diabetol. 2002;39:215–20.CrossRefPubMedGoogle Scholar
Furuya D, Yagihashi A, Nasu S, Endoh T, Nakamura T, Kaneko R, et al. LDL particle size by gradient-gel electrophoresis cannot be estimated by LDL-cholesterol/apolipoprotein B ratios. Clin Chem. 2000;46:1202–3.PubMedGoogle Scholar
Hirayama S, Miida T. Small dense LDL: an emerging risk factor for cardiovascular disease. Clin Chim Acta. 2012;414:215–24.CrossRefPubMedGoogle Scholar
Huang YC, Chang PY, Hwang JS, Ning HC. Association of small dense low density lipoprotein cholesterol in type 2 diabetics with coronary artery disease. Biomed J. 2014;37:375–9.CrossRefPubMedGoogle Scholar
Goel PK, Ashfaq F, Khanna R, Ramesh V, Pandey CM. The association between small dense low density lipoprotein and coronary artery disease in north Indian patients. Indian J Clin Biochem. 2017;32:186–92.CrossRefPubMedGoogle Scholar
Hoogeveen RC, Gaubatz JW, Sun W, Dodge RC, Crosby JR, Jiang J, et al. Small dense low-density lipoprotein-cholesterol concentrations predict risk for coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) study. Arterioscler Thromb Vasc Biol. 2014;34:1069–77.CrossRefPubMedPubMedCentralGoogle Scholar
Matsha TE, Soita DJ, Hassan MS, Hon GM, Yako YY, Kengne AP, et al. Three-year’s changes in glucose tolerance status in the Bellville South cohort: rates and phenotypes associated with progression. Diabetes Res Clin Pract. 2013;99:223–30.CrossRefPubMedGoogle Scholar
Matsha TE, Hassan MS, Kidd M, Erasmus RT. The 30-year cardiovascular risk profile of South Africans with diagnosed diabetes, undiagnosed diabetes, pre-diabetes or normoglycaemia: the Bellville, South Africa pilot study. Cardiovasc J Afr. 2012;23:5–11.CrossRefPubMedPubMedCentralGoogle Scholar
Kikkawa K, Nakajima K, Shimomura Y, Tokita Y, Machida T, Sumino H, et al. Small dense LDL cholesterol measured by homogeneous assay in Japanese healthy controls, metabolic syndrome and diabetes patients with or without a fatty liver. Clin Chim Acta. 2015;438:70–9.CrossRefPubMedGoogle Scholar
Sancho-Rodríguez N, Avilés-Plaza FV, Granero-Fernández E, Hernández-Martínez AM, Albaladejo-Otón MD, Martínez-Mernández P, et al. Observational study of lipid profile and LDL particle size in patients with metabolic syndrome. Clin Chim Acta. 2011;10:162.Google Scholar
Suh S, Park HD, Jin SM, Kim HJ, Bae JC, Park SY, et al. Diabetes mellitus, but not small dense low-density lipoprotein, is predictive of cardiovascular disease: a Korean community-based prospective cohort study. J Diabetes Investig. 2013;4:546–51.CrossRefPubMedPubMedCentralGoogle Scholar
International Diabetes Federation. IDF Diabetes Atlas, 7th Edition. 7th edition ed. Brussels: International Diabetes Federation; 2015.Google Scholar