Thrombophilic risk factors for symptomatic peripheral arterial disease.
OBJECTIVE
Peripheral arterial disease (PAD) is a common manifestation of systemic atherosclerosis. Over the last years, several novel mediators relevant to the process of atherogenesis have been identified, but few and conflicting data are available on the possible association with PAD symptoms. The aim of this study was to determine an extended thrombophilic risk profile of patients with symptomatic PAD.


METHODS
Two hundred eighty patients with symptomatic PAD admitted to the Department of Vascular Surgery of the University of Florence were compared with 280 control subjects without PAD, matched for age and gender. The following metabolic and genetic risk factors were evaluated: lipoprotein(a), homocysteine, antiphospholipid antibodies, plasminogen activator inhibitor-1, factor V Leiden mutation, prothrombin variant, and 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism.


RESULTS
Multivariate logistic regression analysis, adjusted for traditional cardiovascular risk factors, showed a significant association between PAD symptoms and prothrombin variant, altered levels of homocysteine, lipoprotein(a), plasminogen activator inhibitor-1, and antiphospholipid antibodies. Moreover, the presence of high levels of lipoprotein(a) and another metabolic risk factor raised the likelihood of PAD symptoms (dyslipidemia and elevated lipoprotein[a]: odds ratio [OR], 29; 95% confidence interval [CI], 6.2 to 136.2; P <.0001; hyperhomocysteinemia and elevated lipoprotein[a]: OR, 37.7; 95% CI, 3.7 to 381.5; P <.0001). A significant correlation between the number of altered thrombophilic parameters and the Fontaine stage was observed ( R = 0.16; P = .006).


CONCLUSIONS
There is an independent association between altered levels of important thrombophilic risk factors and PAD symptoms. The clinical significance of this association needs to be tested in prospective population-based trials.
Sofi
Francesco
F
Department of Medical and Surgical Critical Care, Thrombosis Centre, University of Florence, Italy. francescosofi@gmail.com
Lari
Barbara
B
Rogolino
Angela
A
Marcucci
Rossella
R
Pratesi
Giovanni
G
Dorigo
Walter
W
Pratesi
Carlo
C
Gensini
Gian Franco
GF
Abbate
Rosanna
R
Prisco
Domenico
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017152:Antibodies, Antiphospholipid / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D005165:Factor V / Q000032:analysis / Q000235:genetics; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D017270:Lipoprotein(a) / Q000097:blood; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D016491:Peripheral Vascular Diseases / Q000097:blood* / Q000235:genetics / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011110:Polymorphism, Genetic; D011516:Prothrombin / Q000032:analysis / Q000235:genetics; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood* / Q000235:genetics / Q000378:metabolism
D017152:Antibodies, Antiphospholipid; D017270:Lipoprotein(a); D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D006710:Homocysteine; D005165:Factor V; D011516:Prothrombin; D042965:Methylenetetrahydrofolate Reductase (NADPH2)