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 Boekholdt, Benoit Arsenault, Gerald Hovingh, Samia Mora, Terje Pedersen, John LaRosa, K Welch, Pierre Amarenco, David DeMicco, Andrew Tonkin, David Sullivan, Adrienne Kirby, Helen Colhoun, Graham Hitman, D Betteridge, Paul Durrington, Michael Clearfield, John Downs, Antonio Gotto, Paul RidkerJohn Kastelein

    Research output: Contribution to journalArticlepeer-review

    118 Citations (Scopus)

    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
    Pages (from-to)1504-1512
    Number of pages9
    JournalCirculation
    Volume128
    Issue number14
    DOIs
    Publication statusPublished - 1 Oct 2013

    Keywords

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

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