Sex-based differences in the inflammatory profile of peripheral artery disease and the association with primary patency of lower extremity vein bypass grafts

Division of Vascular and Endovascular Surgery, University of California-San Francisco, San Francisco, CA 94143-0222, USA.
Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter (Impact Factor: 3.02). 05/2012; 56(2):387-95; discussion 395. DOI: 10.1016/j.jvs.2012.01.059
Source: PubMed

ABSTRACT This study was conducted to determine if there are sex-based differences in the inflammatory phenotype of patients undergoing lower extremity bypass (LEB) and if they correlate with clinical outcomes.
This was a retrospective analysis of a prospective cohort of 225 patients (161 men and 64 women) who underwent autogenous vein LEB between February 2004 and May 2008. Fasting baseline blood samples were obtained before LEB, and the inflammatory biomarkers high-sensitivity C-reactive protein (CRP) and fibrinogen were assessed. All patients underwent ultrasound graft surveillance. CRP levels were dichotomized at 5 mg/L and fibrinogen levels at 600 mg/dL.
There were no significant differences in age, race, history of hypertension or diabetes mellitus, body mass index, or coronary artery disease between men and women. Men were more likely to be current smokers (P = .02), have a history of hypercholesterolemia (P = .02), and be taking statins (P = .02). Women were more likely to present with critical limb ischemia (P = .03) and had higher median baseline CRP levels (5.15 mg/L; interquartile range [IQR], 1.51-18.62 mg/L) than men (2.70; IQR, 1.24-6.98 mg/L; P = .02). Median follow-up was 893 days (IQR, 539-1315 days). A multivariable Cox proportional hazards model for primary vein graft patency showed a significant interaction between sex and CRP (P = .03) and fibrinogen (P = .02). After adjustment for key covariates, primary vein graft patency was significantly less in women with CRP >5 mg/L compared with women with CRP <5 mg/L (P = .02). No such difference was seen in men (P = .95). Primary graft patency was also decreased in women with fibrinogen >600 mg/dL vs women with fibrinogen <600 mg/dL (P = .002); again, this pattern was not evident in men (P = .19).
Women undergoing LEB for advanced peripheral artery disease have a different inflammatory phenotype than men. Elevated baseline levels of CRP and fibrinogen are associated with inferior vein graft patency in women but not in men. These findings indicate an important interaction between sex and inflammation in the healing response of vein grafts for LEB. Women with elevated preoperative CRP and fibrinogen levels may benefit from more intensive postoperative graft surveillance protocols.

1 Read
  • [Show abstract] [Hide abstract]
    ABSTRACT: After the creation of an autogenous lower extremity bypass graft, the vein must undergo a series of dynamic structural changes to stabilize the arterial hemodynamic forces. These changes, which are commonly referred to as remodeling, include an inflammatory response, the development of a neointima, matrix turnover, and cellular proliferation and apoptosis. The sum total of these processes results in dramatic alterations in the physical and biomechanical attributes of the arterialized vein. The most clinically obvious and easily measured of these is lumen remodeling of the graft. However, although somewhat less precise, wall thickness, matrix composition, and endothelial changes can be measured in vivo within the healing vein graft. Recent translational work has demonstrated the clinical relevance of remodeling as it relates to vein graft patency and the systemic factors influencing it. By correlating histologic and molecular changes in the vein, insights into potential therapeutic strategies to prevent bypass failure and areas for future investigation are explored.
    Journal of vascular surgery: official publication, the Society for Vascular Surgery [and] International Society for Cardiovascular Surgery, North American Chapter 10/2013; 61(1). DOI:10.1016/j.jvs.2013.08.019 · 3.02 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Some contend that gender differences in outcomes after lower extremity bypass (LEB) for peripheral arterial disease (PAD) relate to socioeconomic factors (SEFs). Here, we evaluate these disparities with attention to clinically relevant yet understudied SEF. A retrospective cohort study of patients aged >50 y with PAD undergoing LEB was performed using data from Pennsylvania Health care and Cost Containment Council (2003-2011). Multivariable logistic regression modeling was performed to evaluate the association between gender and outcomes with adjustment for potential confounders including SEF such as income, insurance provider, distance to hospital, and race. Generalized estimating equations were used to adjust for hospital clustering. Independent models were developed to examine death or serious morbidity (DSM) and failure-to-rescue (FTR). Of 4202 patients identified, 1510 (36%) were women. SEF differed by gender. DSM was more frequent in women (15.6% versus 12.2%; P = 0.002). There was no association between gender and FTR in univariate analysis (P = 0.49). SEFs were associated with DSM and FTR. After adjustment for potential confounders including SEF, women remained more likely to experience DSM (odds ratio = 1.28; P = 0.01). There remained no significant association between gender and FTR on independent modeling (odds ratio = 0.49; P = 0.11). Women undergoing LEB in the state of Pennsylvania are at increased risk of poor outcomes, which is not completely explained by SEF. Quality of postoperative care does not appear to be different between gender as there was no difference in FTR. To improve these outcomes, efforts should be made to increase awareness of PAD and promote screening among high-risk women to ensure timely diagnosis and referral.
    Journal of Surgical Research 01/2014; 188(2). DOI:10.1016/j.jss.2014.01.043 · 1.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Die folgende Übersicht nimmt zu geschlechtsspezifischen Unterschieden hinsichtlich Prävalenz, Epidemiologie, Risikofaktoren und Therapie bei Patienten mit peripherer arterieller Verschlusskrankheit (PAVK) Stellung.Die Literaturübersicht beruht auf einer Recherche einschlägiger Studien zur PAVK bis Dezember 2013 in der Datenbank Medline (PubMed). Hierfür wurden die Schlüsselwörter ,,periphere arterielle Verschlusskrankheit“, ,,Geschlecht“, ,,Bypass“, ,,Intervention“ und ,,Outcome“ verwendet.Frauen haben ein höheres altersadjustiertes Risiko für eine PAVK. Die Erkrankung verläuft bei ihnen oft symptomfrei, weshalb sie erst in einem fortgeschrittenen Stadium behandelt wird. Ferner erhalten Frauen seltener sekundärprophylaktische Maßnahmen oder eine interventionelle bzw. operative Versorgung. Zudem erleiden sie häufiger ein Bypassversagen, Wundheilungsstörungen, Blutungskomplikationen oder eine Amputation. Studien nach infrainguinaler Rekonstruktion zeigen andererseits vergleichbare Offenheits- und Beinerhaltungsraten wie bei Männern. Auch nach interventioneller Versorgung sind die Unterschiede nur marginal.Ursächlich für die geschlechtsspezifischen Unterschiede könnten neben dem geschlechtsspezifischen kardiovaskulären Risikoprofil auch die Östrogenkonzentration sowie die unterschiedlichen anatomischen Gegebenheiten mit differentem Gefäßkaliber sein.Bei der PAVK gibt es geschlechtsspezifische Unterschiede. Klare leitliniengerechte geschlechtsspezifische Therapieempfehlungen fehlen bislang noch. Sie wären für den langfristigen Therapieerfolg jedoch bedeutsam.
    Gefässchirurgie 03/2014; 19(2). DOI:10.1007/s00772-013-1270-1 · 0.24 Impact Factor
Show more