Cardiovascular and Cancer Events in Hyper-high-density Lipoprotein Cholesterolemic Patients: a Post Hoc Analysis of the MEGA Study

Overview

Journal Lipids Health Dis

Publisher Biomed Central

Specialties Biochemistry
Endocrinology

Date 2014 Aug 20

PMID 25135178

Citations 1

Authors

Haruo Nakamura

Kyoichi Mizuno

Affiliations

Soon will be listed here.

Abstract

Background: The prognosis for hyper-high-density lipoprotein (HDL) cholesterolemic patients has not been fully elucidated. We conducted a post hoc analysis of MEGA study data to investigate prospectively the incidence of cardiovascular events and cancer in hyper-HDL cholesterolemic patients.

Methods: A total of 7832 patients with mild hypercholesterolemia were randomly allocated to either the National Cholesterol Education Program step 1 diet alone (n = 3966) or the diet plus pravastatin (n = 3866) and followed for 5 years. The incidences of coronary heart disease (CHD), CHD plus cerebral infarction (CI), cardiovascular disease (CVD), and cancer were calculated using the Cox proportional hazards model according to the level of HDL cholesterol (HDL-C).

Results: CHD incidence was lower in patients with HDL-C >60-90 mg/dL (-52%, p = 0.0018) and HDL-C > 90 mg/dL (-46%, p = 0.4007) than in patients with HDL-C ≤ 60 mg/dL. The incidences of CHD, CHD plus CI, and CVD were significantly lower in patients with HDL-C >60-90 mg/dL than in those with HDL-C ≤ 60 mg/dL in both diet-alone and diet-plus-pravastatin groups. Cancer incidence was not increased in patients with HDL-C >60-90 mg/dL.

Conclusion: Patients not receiving statin therapy should aim for a target HDL-C of between 60 and 90 mg/dL to achieve a significant reduction in CHD without the occurrence of adverse events.

Trial Registration: Clinical trials.gov NCT00211705.

Citing Articles

Isolated low levels of high-density lipoprotein cholesterol and stroke incidence: JMS Cohort Study.

Watanabe J, Kakehi E, Kotani K, Kayaba K, Nakamura Y, Ishikawa S J Clin Lab Anal. 2019; 34(3):e23087.

PMID: 31742753 PMC: 7083490. DOI: 10.1002/jcla.23087.

References

Nagano M, Yamashita S, Hirano K, Ito M, Maruyama T, Ishihara M . Two novel missense mutations in the CETP gene in Japanese hyperalphalipoproteinemic subjects: high-throughput assay by Invader assay. J Lipid Res. 2002; 43(7):1011-8. DOI: 10.1194/jlr.m200024-jlr200. View

Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray K, Thompson A . Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009; 302(18):1993-2000. PMC: 3284229. DOI: 10.1001/jama.2009.1619. View

Castro-Perez J, Briand F, Gagen K, Wang S, Chen Y, McLaren D . Anacetrapib promotes reverse cholesterol transport and bulk cholesterol excretion in Syrian golden hamsters. J Lipid Res. 2011; 52(11):1965-73. PMC: 3196228. DOI: 10.1194/jlr.M016410. View

Vasan R, Pencina M, Robins S, Zachariah J, Kaur G, DAgostino R . Association of circulating cholesteryl ester transfer protein activity with incidence of cardiovascular disease in the community. Circulation. 2009; 120(24):2414-20. PMC: 2818786. DOI: 10.1161/CIRCULATIONAHA.109.872705. View

Krauss R, Wojnooski K, Orr J, Geaney J, Pinto C, Liu Y . Changes in lipoprotein subfraction concentration and composition in healthy individuals treated with the CETP inhibitor anacetrapib. J Lipid Res. 2011; 53(3):540-547. PMC: 3276477. DOI: 10.1194/jlr.M018010. View

Moriyama Y, Okamura T, Inazu A, Doi M, Iso H, Mouri Y . A low prevalence of coronary heart disease among subjects with increased high-density lipoprotein cholesterol levels, including those with plasma cholesteryl ester transfer protein deficiency. Prev Med. 1998; 27(5 Pt 1):659-67. DOI: 10.1006/pmed.1998.0340. View

Inazu A, Brown M, Hesler C, Agellon L, Koizumi J, Takata K . Increased high-density lipoprotein levels caused by a common cholesteryl-ester transfer protein gene mutation. N Engl J Med. 1990; 323(18):1234-8. DOI: 10.1056/NEJM199011013231803. View

Thompson A, Di Angelantonio E, Sarwar N, Erqou S, Saleheen D, Dullaart R . Association of cholesteryl ester transfer protein genotypes with CETP mass and activity, lipid levels, and coronary risk. JAMA. 2008; 299(23):2777-88. DOI: 10.1001/jama.299.23.2777. View

Voight B, Peloso G, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen M . Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study. Lancet. 2012; 380(9841):572-80. PMC: 3419820. DOI: 10.1016/S0140-6736(12)60312-2. View

10.

Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T . Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006; 368(9542):1155-63. DOI: 10.1016/S0140-6736(06)69472-5. View

11.

Maruyama T, Sakai N, Ishigami M, Hirano K, Arai T, Okada S . Prevalence and phenotypic spectrum of cholesteryl ester transfer protein gene mutations in Japanese hyperalphalipoproteinemia. Atherosclerosis. 2002; 166(1):177-85. DOI: 10.1016/s0021-9150(02)00327-1. View

12.

Baigent C, Blackwell L, Emberson J, Holland L, Reith C, Bhala N . Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376(9753):1670-81. PMC: 2988224. DOI: 10.1016/S0140-6736(10)61350-5. View

13.

FRIEDEWALD W, Levy R, Fredrickson D . Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972; 18(6):499-502. View

14.

Curb J, Abbott R, Rodriguez B, Masaki K, Chen R, Sharp D . A prospective study of HDL-C and cholesteryl ester transfer protein gene mutations and the risk of coronary heart disease in the elderly. J Lipid Res. 2004; 45(5):948-53. DOI: 10.1194/jlr.M300520-JLR200. View

15.

Zhong S, Sharp D, Grove J, Bruce C, Yano K, Curb J . Increased coronary heart disease in Japanese-American men with mutation in the cholesteryl ester transfer protein gene despite increased HDL levels. J Clin Invest. 1996; 97(12):2917-23. PMC: 507389. DOI: 10.1172/JCI118751. View

16.

Nielsen S, Nordestgaard B, Bojesen S . Statin use and reduced cancer-related mortality. N Engl J Med. 2012; 367(19):1792-802. DOI: 10.1056/NEJMoa1201735. View