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Role of Lipoprotein-Associated Phospholipase A2 in Predicting Risk of Cardiovascular Disease

      To the Editor: In their editorial accompanying the meta-analysis of lipoprotein-associated phospholipase A2 (Lp-PLA2) by Garza et al,
      • Garza CA
      • Montori VM
      • McConnell JP
      • Somers VK
      • Kullo IJ
      • Lopez-Jimenez F
      Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review.
      Steinberg and Mayer
      • Steinberg DI
      • Mayer A
      Lipoprotein-associated phospholipase A2 and risk stratification for cardiovascular disease: not ready for “prime time” [editorial].
      brought up important points regarding the use of markers to predict risk of cardiovascular disease (CVD) before solid evidence is available to support such use. Although Lp-PLA2 is indeed considered a “novel risk factor,” I believe the authors made an incomplete and inaccurate statement about the role that Lp-PLA2 may play in the prediction of myocardial infarction and stroke, both of which are major components of CVD.
      The Atherosclerosis Risk in Communities (ARIC) study suggested that Lp-PLA2 is a moderately strong predictor of risk of stroke and that the association between Lp-PLA2 and stroke is statistically independent of traditional risk factors.
      • Ballantyne CM
      • Hoogeveen RC
      • Bang H
      • et al.
      Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the atherosclerosis risk in communities (ARIC) Study.
      This study, as well as several others examining Lp-PLA2 and stroke, was neither mentioned in the editorial nor included in the meta-analysis. In fact, Garza et al
      • Garza CA
      • Montori VM
      • McConnell JP
      • Somers VK
      • Kullo IJ
      • Lopez-Jimenez F
      Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review.
      did not include the term stroke in their literature search; an omission that would undoubtedly affect the authors' findings. Of note, the US Food and Drug Administration has approved the PLAC test for measurement of Lp-PLA2 to predict stroke.
      Interestingly, Steinberg and Mayer
      • Steinberg DI
      • Mayer A
      Lipoprotein-associated phospholipase A2 and risk stratification for cardiovascular disease: not ready for “prime time” [editorial].
      used high-sensitivity C-reactive protein as a comparator to Lp-PLA2. C-reactive protein is an acute phase reactant and inflammatory marker that has been shown to be a predictor of CVD risk. However, C-reactive protein elevation is not specific for CVD and may be present in other disorders as well. Lipoprotein-associated phospholipase A2 is an enzyme (platelet-activating factor acetylhydrolase) that is bound to low-density lipoprotein cholesterol. Although the precise mechanisms by which Lp-PLA2 confers risk have not been completely delineated, it appears to be relatively specific for CVD risk.
      • Lanman RB
      • Wolfert RL
      • Fleming JK
      • et al.
      Lipoprotein-associated phospholipase A2: review and recommendation of a clinical cut point for adults.
      Finally, while I agree that the Framingham Risk Score has certainly held its own over the years, I disagree with the authors' assertion that busy clinicians should use this tool for risk stratification. Many other factors can add to the predictive value of the Framingham score. Risk prediction is currently a very good, but not perfect, science. Undoubtedly, refinement of currently available methods will ultimately allow physicians to better determine who is at low or high risk for a CVD event. As novel factors emerge, we need to carefully evaluate all the evidence to support clinical applications. In their editorial, Steinberg and Mayer unfortunately took an incomplete look at Lp-PLA2.

      REFERENCES

        • Garza CA
        • Montori VM
        • McConnell JP
        • Somers VK
        • Kullo IJ
        • Lopez-Jimenez F
        Association between lipoprotein-associated phospholipase A2 and cardiovascular disease: a systematic review.
        Mayo Clin Proc. 2007; 82: 159-165
        • Steinberg DI
        • Mayer A
        Lipoprotein-associated phospholipase A2 and risk stratification for cardiovascular disease: not ready for “prime time” [editorial].
        Mayo Clin Proc. 2007; 82: 155-157
        • Ballantyne CM
        • Hoogeveen RC
        • Bang H
        • et al.
        Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the atherosclerosis risk in communities (ARIC) Study.
        Arch Intern Med. 2005; 165: 2479-2484
        • Lanman RB
        • Wolfert RL
        • Fleming JK
        • et al.
        Lipoprotein-associated phospholipase A2: review and recommendation of a clinical cut point for adults.
        Prev Cardiol. 2006 Summer; 9: 138-143

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