A meta-analysis of potential risks of low levels of protein Z for diseases related to vascular thrombosis

Abstract

The relationship between protein Z levels and thrombosis is controversial. We performed a systematic review and meta-analysis of the available studies to assess the association between protein Z and vascular thrombotic diseases. We conducted an electronic literature search through MedLine, Embase, Google Scholar, Web of Science, The Cochrane Library, bibliographies of retrieved articles and abstracts of congresses up to October, 2009. Studies were included if they analysed protein Z levels in patients with vascular thrombotic diseases. After the review process, 28 case-control studies (33 patient cohorts), including 4,218 patients with thrombotic diseases and 4,778 controls, were selected for analysis. The overall analysis using a random-effects model showed that low protein Z levels were associated with an increased risk of thrombosis (odds ratio [OR] 2.90, 95% confidence interval [CI] 2.05-4.12; p<0.00001). On subgroup analysis, a significant association was found between low protein Z levels and arterial vascular diseases (OR 2.67, 95%CI 1.60-4.48; p=0.0002), pregnancy complications (OR 4.17, 95%CI 2.31-7.52; p<0.00001), and venous thromboembolic diseases (OR 2.18, 95%CI 1.19-4.00; p=0.01). The results of this meta-analysis are consistent with a role for protein Z deficiency in thrombotic diseases, including arterial thrombosis, pregnancy complications and venous thromboembolism.

Figure 1

Flow chart of search strategy.

Figure 2. Risk of vascular thrombotic diseases for low protein Z levels

Squares represent the effect size; extended lines, 95%CI; diamond, total effect size. IS, ischaemic stroke; DVT, deep-vein thrombosis; ACS, acute coronary syndromes; CAD, coronary artery disease; PE, preeclampsia; FL, fetal loss; ART, arterial vascular diseases; VEN, venous thromboembolic diseases.

Figure 3. Risk of arterial vascular diseases for low protein Z levels

Squares represent the effect size; extended lines, 95%CI; diamond, total effect size. IS, ischaemic stroke; ACS, acute coronary syndromes; CAD, coronary artery disease; ART, arterial vascular diseases.

Figure 4. Risk of pregnancy complications for low protein Z levels

Squares represent the effect size; extended lines, 95%CI; diamond, total effect size. PE, preeclampsia; FL, fetal loss.

Figure 5. Risk of venous thromboembolic diseases for low protein Z levels

Squares represent the effect size; extended lines, 95%CI; diamond, total effect size.

Figure 6. Subgroup analyses

Squares represent the effect size; extended lines, 95%CI; diamond, total effect size.