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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

Comparison between the median thrombin generation activity curves in groups stratified on the basis of number of procoagulant alleles, with a threshold level at 5 alleles.
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pone-0001523-g003: Comparison between the median thrombin generation activity curves in groups stratified on the basis of number of procoagulant alleles, with a threshold level at 5 alleles.

Mentions: To get insights on the pathophysiological effect of combined hemostatic alleles, we assessed the characteristics of thrombin generation activity curves as a function of the number of procoagulant alleles (i.e. fibrinogen β-chain -455 A, Prothrombin 20210 A, Factor V Leiden, Factor V R2, Factor VII A1, Factor VII -402 A and PAI-1 -675 4G). Since this assay pertains only to the coagulation pathway, the three platelet-related polymorphisms were not considered for this analysis. This assay was performed in a subset of 29 CAD patients (26 males and 3 females, 22 with and 7 without MI), selected among those without possible confounders (i.e. concomitant anticoagulant therapy or overt signs of inflammation, documented by hs-CRP<5 mg/l), in order to form three groups matched for age and sex representing the previously defined risk groups (low-risk: n = 9, 8 males and 1 female, mean age 53.7±8.5; intermediate-risk: n = 10, 9 males and 1 female, mean age 57.8±7.4; high-risk: n = 10, 9 males and 1 female, mean age 56.0±8.6). The number of procoagulant alleles was significantly associated with ETP and with Start Tail, but not with Lag Time, Peak or Time to Peak (Table 3). Similarly, subjects with a high number of procoagulant alleles (≥5) had significantly higher ETP values as compared to subjects with fewer alleles (Table 4). These two groups were similar not only for age and sex, but also for smoking, hypertension and diabetes (data not shown). Their median thrombin generation activity curves are showed in Figure 3.


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)

Comparison between the median thrombin generation activity curves in groups stratified on the basis of number of procoagulant alleles, with a threshold level at 5 alleles.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0001523-g003: Comparison between the median thrombin generation activity curves in groups stratified on the basis of number of procoagulant alleles, with a threshold level at 5 alleles.
Mentions: To get insights on the pathophysiological effect of combined hemostatic alleles, we assessed the characteristics of thrombin generation activity curves as a function of the number of procoagulant alleles (i.e. fibrinogen β-chain -455 A, Prothrombin 20210 A, Factor V Leiden, Factor V R2, Factor VII A1, Factor VII -402 A and PAI-1 -675 4G). Since this assay pertains only to the coagulation pathway, the three platelet-related polymorphisms were not considered for this analysis. This assay was performed in a subset of 29 CAD patients (26 males and 3 females, 22 with and 7 without MI), selected among those without possible confounders (i.e. concomitant anticoagulant therapy or overt signs of inflammation, documented by hs-CRP<5 mg/l), in order to form three groups matched for age and sex representing the previously defined risk groups (low-risk: n = 9, 8 males and 1 female, mean age 53.7±8.5; intermediate-risk: n = 10, 9 males and 1 female, mean age 57.8±7.4; high-risk: n = 10, 9 males and 1 female, mean age 56.0±8.6). The number of procoagulant alleles was significantly associated with ETP and with Start Tail, but not with Lag Time, Peak or Time to Peak (Table 3). Similarly, subjects with a high number of procoagulant alleles (≥5) had significantly higher ETP values as compared to subjects with fewer alleles (Table 4). These two groups were similar not only for age and sex, but also for smoking, hypertension and diabetes (data not shown). Their median thrombin generation activity curves are showed in Figure 3.

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