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Combined effect of hemostatic gene polymorphisms and the risk of myocardial infarction in patients with advanced coronary atherosclerosis.

Martinelli N, Trabetti E, Pinotti M, Olivieri O, Sandri M, Friso S, Pizzolo F, Bozzini C, Caruso PP, Cavallari U, Cheng S, Pignatti PF, Bernardi F, Corrocher R, Girelli D - PLoS ONE (2008)

Bottom Line: In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors.As compared to subjects with 3-7 alleles, those with few (</=2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13-0.93), while those with more (>/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01).The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy.

ABSTRACT

Background: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI.

Methodology/principal findings: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential.

Conclusions: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.

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Related in: MedlinePlus

OR for MI in groups stratified on the basis of number of unfavourable alleles.The intermediate group (from 3 to 7 unfavourable prothrombotic alleles), representing the 85.3% of the whole population, is considered as reference group.
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pone-0001523-g002: OR for MI in groups stratified on the basis of number of unfavourable alleles.The intermediate group (from 3 to 7 unfavourable prothrombotic alleles), representing the 85.3% of the whole population, is considered as reference group.

Mentions: No significant interaction was found by CART among polymorphisms in determining MI risk (all P for interaction >0.05). As shown in figure 1C, the proportion of CAD patients with MI increased progressively with increasing number of unfavourable alleles (χ2 for linear trend = 10.68; P = 0.001). In a multiple logistic regression model the prothrombotic score remained significantly associated with MI after adjustment for sex, age, degree of CAD, smoke, BMI, LDL- and HDL-cholesterol (OR for 1-point increase in prothrombotic score = 1.22 with 95%CI 1.06–1.39, P = 0.004). Using the median of PS as cut-off, CAD patients with >5 alleles had a significantly increased risk of MI as compared to subjects with ≤5 alleles (OR 2.02 with 95%CI 1.27–3.21, P = 0.003, by multiple logistic regression). Using approximately the 5th and the 95th percentiles of PS distribution (i.e. 2 and 8, respectively), the study population could be classified into in 3 subgroups: a low-risk group with less than 3 unfavourable alleles (n = 26), an intermediate-risk group with 3 to 7 unfavourable alleles (n = 417), and a high-risk group with more than 7 unfavourable alleles (n = 46). The prevalence of MI among these groups increased progressively (38.5% in low-risk; 62.6% in intermediate-risk; and 78.3% in high-risk; P = 0.001 by χ2 for linear trend), while they were similar for the other clinical and laboratory variables (data not shown). Considering the intermediate-risk group as the reference group, carriers of <3 alleles had a lower risk of MI, while carriers of >7 alleles had an increased risk (Figure 2). Comparing the two extreme groups, the subjects with >7 alleles had a remarkably higher MI risk (OR 7.28 with 95%CI 2.01–26.36, P = 0.002 adjusted by multiple logistic regression). The ROC curve for information provided by our polygenic approach for MI prediction in CAD patients is plotted in Supplemental Figure 1 (Figure S1). The AUC was 0.581 with a 95% CI from 0.530 to 0.632.


Combined effect of hemostatic gene polymorphisms and the risk of myocardial infarction in patients with advanced coronary atherosclerosis.

Martinelli N, Trabetti E, Pinotti M, Olivieri O, Sandri M, Friso S, Pizzolo F, Bozzini C, Caruso PP, Cavallari U, Cheng S, Pignatti PF, Bernardi F, Corrocher R, Girelli D - PLoS ONE (2008)

OR for MI in groups stratified on the basis of number of unfavourable alleles.The intermediate group (from 3 to 7 unfavourable prothrombotic alleles), representing the 85.3% of the whole population, is considered as reference group.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211406&req=5

pone-0001523-g002: OR for MI in groups stratified on the basis of number of unfavourable alleles.The intermediate group (from 3 to 7 unfavourable prothrombotic alleles), representing the 85.3% of the whole population, is considered as reference group.
Mentions: No significant interaction was found by CART among polymorphisms in determining MI risk (all P for interaction >0.05). As shown in figure 1C, the proportion of CAD patients with MI increased progressively with increasing number of unfavourable alleles (χ2 for linear trend = 10.68; P = 0.001). In a multiple logistic regression model the prothrombotic score remained significantly associated with MI after adjustment for sex, age, degree of CAD, smoke, BMI, LDL- and HDL-cholesterol (OR for 1-point increase in prothrombotic score = 1.22 with 95%CI 1.06–1.39, P = 0.004). Using the median of PS as cut-off, CAD patients with >5 alleles had a significantly increased risk of MI as compared to subjects with ≤5 alleles (OR 2.02 with 95%CI 1.27–3.21, P = 0.003, by multiple logistic regression). Using approximately the 5th and the 95th percentiles of PS distribution (i.e. 2 and 8, respectively), the study population could be classified into in 3 subgroups: a low-risk group with less than 3 unfavourable alleles (n = 26), an intermediate-risk group with 3 to 7 unfavourable alleles (n = 417), and a high-risk group with more than 7 unfavourable alleles (n = 46). The prevalence of MI among these groups increased progressively (38.5% in low-risk; 62.6% in intermediate-risk; and 78.3% in high-risk; P = 0.001 by χ2 for linear trend), while they were similar for the other clinical and laboratory variables (data not shown). Considering the intermediate-risk group as the reference group, carriers of <3 alleles had a lower risk of MI, while carriers of >7 alleles had an increased risk (Figure 2). Comparing the two extreme groups, the subjects with >7 alleles had a remarkably higher MI risk (OR 7.28 with 95%CI 2.01–26.36, P = 0.002 adjusted by multiple logistic regression). The ROC curve for information provided by our polygenic approach for MI prediction in CAD patients is plotted in Supplemental Figure 1 (Figure S1). The AUC was 0.581 with a 95% CI from 0.530 to 0.632.

Bottom Line: In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors.As compared to subjects with 3-7 alleles, those with few (</=2) alleles had a decreased MI risk (OR 0.34, 95%CIs 0.13-0.93), while those with more (>/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01).The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical and Experimental Medicine, University of Verona, Verona, Italy.

ABSTRACT

Background: Relative little attention has been devoted until now to the combined effects of gene polymorphisms of the hemostatic pathway as risk factors for Myocardial Infarction (MI), the main thrombotic complication of Coronary Artery Disease (CAD). The aim of this study was to evaluate the combined effect of ten common prothrombotic polymorphisms as a determinant of MI.

Methodology/principal findings: We studied a total of 804 subjects, 489 of whom with angiographically proven severe CAD, with or without MI (n = 307; n = 182; respectively). An additive model considering ten common polymorphisms [Prothrombin 20210G>A, PAI-1 4G/5G, Fibrinogen beta -455G>A, FV Leiden and "R2", FVII -402G>A and -323 del/ins, Platelet ADP Receptor P2Y12 -744T>C, Platelet Glycoproteins Ia (873G>A), and IIIa (1565T>C)] was tested. The prevalence of MI increased linearly with an increasing number of unfavorable alleles (chi(2) for trend = 10.68; P = 0.001). In a multiple logistic regression model, the number of unfavorable alleles remained significantly associated with MI after adjustment for classical risk factors. As compared to subjects with 3-7 alleles, those with few (/=8) alleles had an increased MI risk (OR 2.49, 95%CIs 1.03-6.01). The number of procoagulant alleles correlated directly (r = 0.49, P = 0.006) with endogenous thrombin potential.

Conclusions: The combination of prothrombotic polymorphisms may help to predict MI in patients with advanced CAD.

Show MeSH
Related in: MedlinePlus