Association between change in HDL-C and vascular events in patients treated with statins: Report from the UK general practice research database

Lori D. Bash, Tun-Ying Hsu, Vasilisa Sazonov, Baishali Ambegaonkar

Department of Epidemiology, University of Medicine and Dentistry of New Jersey, Piscataway, USA.
Global Health Outcomes, Merck & Co., Inc., Whitehouse Station, USA.

DOI: 10.4236/wjcd.2012.22011                

Abstract

Dyslipidemia, including low levels of high-density lipoprotein cholesterol (HDL-C), is a relatively well-established risk factor for cardiovascular disease. However, the independent association between changes in HDL-C and the subsequent risk of cardiovascular events has not been well studied. The retrospective cohort analysis was conducted to evaluate the association between changes in HDL-C and cardiovascular (CV) and/or cerebrovascular (CB) events among statin-treated patients. Patient demo-graphics, clinical characteristics, laboratory data, and CV/CB events, were collected from the UK General Practice Research Database. The association between the risk of an incident event and changes in patients’ HDL-C was estimated using multivariate Cox pro-portional hazards models. Among 17,923 statin-treated patients with an average follow-up of 1.9 years, there were 815 CV events and 220 CB events. The average change in HDL-C experienced was 0.4 mg/dL, ranging from 11 mg/dL average decrease in the lowest change quartile to 12 mg/dL average increase in the highest change quartile. CV events occurred at an average overall rate of 21 per 1000 person-years and 17 per 1000 person-years among individuals in the highest quartile of change in HDL-C levels. Fully adjusted Cox regression estimated a 6% decrease in hazards (HR, 0.94; 95% CI, 0.90, 0.98) of a subsequent CV event associated with each 5 mg/dL increase in HDL-C. Similar results (HR: 0.95, 95% CI, 0.92, 0.98) were observed when assessing the association with changes in HDL-C and the composite outcome of CV/CB event. Among statin-treated patients from UK clinical practices, increases in HDL-C were associated with a significantly decreased relative risk of experiencing CV/CB events with a more pronounced effect on CV events. Therefore, a more aggressive treatment to increase HDL-C could benefit patients by reducing the risk of CV/CB events.

Keywords

LDL-C; HDL-C; CV and CB Event and LMT

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	The World Health Organization (2011) The World Health Organization: Cardiovascular diseases. http://www.who.int/mediacentre/factsheets/fs317/en/index.html#
[2]	British Heart Foundation (2010) Coronary heart disease statistics. http://www.bhf.org.uk/idoc.ashx?docid=9ef69170-3edf-4fbb-a202-a93955c1283d&version=-1
[3]	The World Health Organization (2011) The World Health Organization: NCD country profiles: United States of America. http://www.who.int/nmh/countries/usa_en.pdf.
[4]	Lloyd-Jones, D., Adams, R., Carnethon, M., et al. (2009) Heart disease and stroke statistics—2009 update: A report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation, 119, 480-486. doi:10.1161/CIRCULATIONAHA.108.191259
[5]	U.S. Centers for Disease Control and Prevention (2011) National vital statistics reports. http://www.cdc.gov/nchs/data/nvsr/nvsr59/nvsr59_04.pdf
[6]	Erhardt, L.R. and Gotto, A. Jr. (2006) The evolution of European guidelines: Changing the management of cholesterol levels. Atherosclerosis, 185, 12-20. doi:10.1016/j.atherosclerosis.2005.10.001
[7]	Grundy, S.M., Cleeman, J.I., Merz, C.N., et al. (2004) Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. Journal of the American College of Cardiology, 44, 720-732.doi:10.1016/j.jacc.2004.07.001
[8]	Graham, I., Atar, D., Borch-Johnsen, K. et al. (2007) Euro- pean guidelines on cardiovascular disease prevention in clinical practice: Executive summary. European Heart Journal, 28, 2375-2414. doi:10.1093/eurheartj/ehm316
[9]	Sarwar, N., Danesh, J., Eiriksdottir, G., et al. (2007) Triglycerides and the risk of coronary heart disease: 10,158 incident cases among 262,525 participants in 29 western prospective studies. Circulation, 115, 450-458. doi:10.1161/CIRCULATIONAHA.106.637793
[10]	Morrison, A. and Hokanson, J.E. (2009) The independent relationship between triglycerides and coronary heart dis- ease. Vascular Health Risk Management, 5, 89-95.
[11]	Gordon, T., Castelli, W.P., Hjortland, M.C., et al. (1977) High density lipoprotein as a protective factor against coronary heart disease: The Fra-mingham study. American Journal of Medicine, 62, 707-714. doi:10.1016/0002-9343(77)90874-9
[12]	Sharrett, A.R., Bal-lantyne, C.M., Coady, S.A., et al. (2001) Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoproteins A-I and B, and HDL-C density subfractions: The Atherosclerosis Risk in Communities (ARIC) study. Circulation, 104, 1108-1113. doi:10.1161/hc3501.095214
[13]	Miller, M., Cannon, C.P., Murphy, S.A., et al. (2008) Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. Journal of American College of Cardiology, 51, 724-730. doi:10.1016/j.jacc.2007.10.038
[14]	Faergeman, O., Holme, I., Fayyad, R., et al. (2009) Plasma triglycerides and cardiovascular events in the treating to new targets and incremental decrease in end-points through aggressive lipid lowering trials of statins in patients with coronary artery disease. American Journal of Cardiology, 104, 459-463. doi:10.1016/j.amjcard.2009.04.008
[15]	Barter, P., Gotto, A.M., LaRosa, J.C., et al. (2007) HDL- C cholesterol, very low levels of LDL cholesterol, and cardiovascular events. New England Journal of Medicine, 357, 1301-1310. doi:10.1056/NEJMoa064278
[16]	Shanthi, M., Puska, P. and Norrving, B. (2011) Global Atlas on cardiovascular disease prevention and control. http://whqlibdoc.who.int/publications/2011/9789241564373_eng.pdf
[17]	Gordon, T., Kannel, W.B., Castelli, W.P., et al. (1981) Lipoproteins, cardiovascular disease, and death: The Fram- ingham study. Archives of Internal Medicine, 141, 1128- 1131. doi:10.1001/archinte.1981.00340090024008
[18]	Kini, A.S., Muntner, P., Moreno, P.R., et al. (2009) Relation of high-density lipoprotein cholesterol to mortality after percuta-neous coronary interventions in patients with low-density lipoprotein <70 mg/dl. American Journal of Cardiolology, 103, 350-354. doi:10.1016/j.amjcard.2008.09.087
[19]	Rywik, S.L., Manolio, T.A., Pajak, A., et al. (1999) As- sociation of lipids and lipoprotein level with total mortality and mortality caused by cardiovascular and cancer diseases (Poland and United States collaborative study on cardiovascular epidemiology). American Journal of Cardiolology, 84, 540-548. doi:10.1016/S0002-9149(99)00374-4
[20]	Ghazzal, Z.B., Dhawan, S.S., Sheikh, A., et al. (2009) Usefulness of serum high-density lipoprotein cholesterol level as an independent predictor of one-year mortality after percutaneous coronary interventions. American Journal of Cardiolology, 103, 902-906. doi:10.1016/j.amjcard.2008.11.053
[21]	Goldenberg, I., Benderly, M., Sidi, R., et al. (2009) Relation of clinical benefit of raising high-density lipoprotein cholesterol to serum levels of low-density lipoprotein cholesterol in patients with coronary heart disease (from the Bezafibrate infarction prevention trial). American Journal of Cardiolology, 103, 41-45. doi:10.1016/j.amjcard.2008.08.033
[22]	Bittner, V., Johnson, B.D., Zineh, I., et al. (2009) The triglyceride/high-density lipo-protein cholesterol ratio predicts all-cause mortality in women with suspected myocardial ischemia: A report from the Women’s Ischemia Syndrome Evaluation (WISE). Americn Heart Journal, 157, 548-555. doi:10.1016/j.ahj.2008.11.014
[23]	Cui, Y., Watson, D.J., Girman, C.J., et al. (2009) Effects of increasing high-density lipoprotein cholesterol and decreasing low-density lipoprotein cholesterol on the incidence of first acute coronary events (from the Air Force/ Texas Coronary Atherosclerosis Prevention Study). American Journal of Cardiolology, 104, 829-834. doi:10.1016/j.amjcard.2009.05.020
[24]	Arsenault B., Barter P., DeMicco D., et al. (2011) Prediction of cardiovascular events in statin-treated stable coronary patients by lipid and nonlipid biomarkers. Journal of American College of Cardiolology, 57, 63-69. doi:10.1016/j.jacc.2010.06.052
[25]	Sazonov, V., Beetsch, J., Phatak, H., et al. (2010) Association between dyslipidemia and vascular events in patients treated with statins: Report from the UK General Practice Research Database. Atherosclerosis, 208, 210- 216. doi:10.1016/j.atherosclerosis.2009.07.021
[26]	Walley, T. and Mantgani, A. (1997) The UK general practice research database. Lancet, 350, 1097-1099. doi:10.1016/S0140-6736(97)04248-7
[27]	Jick, S.S., Kaye, J.A., Vasilakis-Scaramozza, C., et al. (2003) Validity of the general practice research database. Phar- macotherapy, 23, 686-689. doi:10.1592/phco.23.5.686.32205
[28]	Waters, D. (1999) Cholesterol lowering: Should it continue to be the last thing we do? Circulation, 99, 3215- 3217.
[29]	Grover, S., Kaouache, M., Joseph, L., et al. (2009) Evaluating the incremental benefits of raising high-density lipoprotein cholesterol levels during lipid therapy after adjustment for the reductions in other blood lipid levels. Archives of Internal Medicine, 169, 1775-1780. doi:10.1001/archinternmed.2009.328
[30]	Tziomalos, K., Athyros, V.G., Karagiannis, A., et al. (2009) Dyslipidemia as a risk factor for ischemic stroke. Current Topics in Medicinal Chemistry, 9, 1291-1297. doi:10.2174/156802609789869628