High Levels of Apolipoprotein A1 and HDL Associated With Reduced Risk of Recurrent VTE

March 22, 2007

March 22, 2007 (La Jolla, CA) - Patients with high levels of apolipoprotein A1 and HDL cholesterol and large HDL particles have a decreased risk of developing recurrent venous thromboembolism (VTE), a new study has shown [1]. In consecutive patients with a single episode of unprovoked VTE, the risk of recurrence was cut in half in subjects with apolipoprotein-A1 levels exceeding 1.30 mg/mL when compared with subjects who had lower levels.

"The present study is prospective in nature and provides strong evidence for an association of protection against risk of recurrent venous thrombosis with elevated levels of apolipoprotein A1, the major protein component of HDL," write lead author Dr Sabine Eichinger (Medical University of Vienna, Austria) and colleagues in a paper published online March 19, 2007 in Circulation. "This finding may justify further clinical studies to assess whether strategies to elevate HDL using lifestyle changes will reduce risk for venous thrombosis."

While dyslipidemia and dyslipoproteinemia are established risk factors for arterial thrombosis, with lipid-lowering drugs used to prevent ischemic events, the relevance of dyslipoproteinemia for the occurrence of VTE is not clear, the authors write. There is evidence, though, they add, that venous and arterial thrombotic disease share similar risk factors, including age, male sex, elevated body weight, lupus anticoagulant, and elevated homocysteine levels.

With this in mind, investigators sought to examine the association between HDL-cholesterol levels and recurrent VTE. Using data from the ongoing Austrian Study of Recurrent Venous Thromboembolism (AUREC), Eichinger and colleagues studied 772 patients with a first spontaneous VTE. Average follow-up was 48 months, and recurrent VTE developed in 100 of the 772 patients.

Overall, patients with a recurrent VTE had significantly lower levels of apolipoprotein A1 than those without recurrence. When investigators entered apolipoprotein A1 as a continuous variable in a Cox proportional hazards model, the relative risk of VTE recurrence was 0.87 (95% CI 0.80-0.94) for every 0.1-mg/mL increase in plasma apolipoprotein-A1 levels.

Investigators did not predefine cutoff values for apolipoprotein A1, due to the hypothesis-generating nature of the study, but instead looked at the strength and linearity of the association between apolipoprotein A1 and the risk of recurrence by calculating relative risks for various apolipoprotein-A1 levels. The strongest association between apolipoprotein A1 and recurrent VTE was observed at levels >1.30 mg/mL, which corresponds to the lower limit of the highest tertile in this cohort. In addition, there was a trend for association between recurrence and low levels of HDL particles and HDL cholesterol.

Relative risks of recurrent VTE according to tertiles of apolipoprotein-A1 concentrations

Apolipoprotein A1, mg/mL Patients, n Recurrences, n Adjusted relative risk (95% CI)
<1.07 243 43 1.0
1.07–1.30 267 36 0.76 (0.48–1.21)
>1.30 262 21 0.50 (0.28–0.88)

Eichinger and colleagues point out that male sex is an independent risk factor for VTE recurrence, conveying a fourfold greater risk than being female. In this study, apolipoprotein-A1 levels were significantly lower among men than women, suggesting the protective properties of HDL cholesterol might explain this difference between the sexes. The authors write,however, that these results warrant further study, including replication in other patient populations, especially to determine whether one or more HDL parameters might be useful to clinicians in assessing the risk of recurrent VTE

  1. Eichinger S, Pecheniuk NM, Hron G, et al. High-density lipoprotein and the risk of recurrent venous thromboembolism. Circulation 2007; 115:1609-1614.

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