Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: A meta-analysis

S. Matthijs Boekholdt, Benoit J. Arsenault, G. Kees Hovingh, Samia Mora, Terje R. Pedersen, John C. Larosa, K. M.A. Welch, Pierre Amarenco, David A. Demicco, Andrew M. Tonkin, David R. Sullivan, Adrienne Kirby, Helen M. Colhoun, Graham A. Hitman, D. John Betteridge, Paul N. Durrington, Michael B. Clearfield, John R. Downs, Antonio M. Gotto, Paul M. RidkerJohn J.P. Kastelein

Research output: Contribution to journalArticle

116 Scopus citations

Abstract

BACKGROUND-: It is unclear whether levels of high-density lipoprotein cholesterol (HDL-C) or apolipoprotein A-I (apoA-I) remain inversely associated with cardiovascular risk among patients who achieve very low levels of low-density lipoprotein cholesterol on statin therapy. It is also unknown whether a rise in HDL-C or apoA-I after initiation of statin therapy is associated with a reduced cardiovascular risk. METHODS AND RESULTS-: We performed a meta-analysis of 8 statin trials in which lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Individual patient data were obtained for 38 153 trial participants allocated to statin therapy, of whom 5387 suffered a major cardiovascular event. HDL-C levels were associated with a reduced risk of major cardiovascular events (adjusted hazard ratio [HR], 0.83; 95% confidence interval [CI], 0.81-0.86 per 1 standard deviation increment), as were apoA-I levels (HR, 0.79; 95% CI, 0.72-0.82). This association was also observed among patients achieving on-statin low-density lipoprotein cholesterol levels <50 mg/dL. An increase of HDL-C was not associated with reduced cardiovascular risk (HR, 0.98; 95% CI, 0.94-1.01 per 1 standard deviation increment), whereas a rise in apoA-I was (HR, 0.93; 95% CI, 0.90-0.97). CONCLUSIONS-: Among patients treated with statin therapy, HDL-C and apoA-I levels were strongly associated with a reduced cardiovascular risk, even among those achieving very low low-density lipoprotein cholesterol. An apoA-I increase was associated with a reduced risk of major cardiovascular events, whereas for HDL-C this was not the case. These findings suggest that therapies that increase apoA-I concentration require further exploration with regard to cardiovascular risk reduction.

Original languageEnglish (US)
Pages (from-to)1504-1512
Number of pages9
JournalCirculation
Volume128
Issue number14
DOIs
StatePublished - Oct 1 2013

Keywords

  • apolipoproteins
  • cardiovascular diseases
  • high-density lipoprotein cholesterol
  • meta-analysis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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    Boekholdt, S. M., Arsenault, B. J., Hovingh, G. K., Mora, S., Pedersen, T. R., Larosa, J. C., Welch, K. M. A., Amarenco, P., Demicco, D. A., Tonkin, A. M., Sullivan, D. R., Kirby, A., Colhoun, H. M., Hitman, G. A., Betteridge, D. J., Durrington, P. N., Clearfield, M. B., Downs, J. R., Gotto, A. M., ... Kastelein, J. J. P. (2013). Levels and changes of HDL cholesterol and apolipoprotein A-I in relation to risk of cardiovascular events among statin-treated patients: A meta-analysis. Circulation, 128(14), 1504-1512. https://doi.org/10.1161/CIRCULATIONAHA.113.002670