An integrated biochemical prediction model of all-cause mortality in patients undergoing lower extremity bypass surgery for advanced peripheral artery disease

Abstract

Background Patients with advanced peripheral artery disease (PAD) have a high prevalence of cardiovascular (CV) risk factors and shortened life expectancy. However, CV risk factors poorly predict midterm (<5 years) mortality in this population. This study was designed to test the hypothesis that baseline biochemical parameters would add clinically meaningful predictive information in patients undergoing lower extremity bypass. Methods This was a prospective cohort study of subjects with clinically advanced PAD undergoing lower extremity bypass surgery. The Cox proportional hazard was used to assess the main outcome of all-cause mortality. A clinical model was constructed with known cardiovascular risk factors and the incremental value of the addition of clinical chemistry, lipid, and a panel of 11 inflammatory parameters were investigated using c-statistic, the integrated discrimination improvement (IDI) index and Akaike information criterion (AIC). Results 225 subjects were followed for a median 893 days; IQR 539–1315 days). In this study 50 (22.22%) subjects died during the follow-up period. By life table analysis (expressed as percent surviving ± standard error), survival at 1, 2, 3, 4, and 5 years respectively was 90.5 ± 1.9%, 83.4 ± 2.5%, 77.5 ± 3.1%, 71.0 ± 3.8%, and 65.3 ± 6.5%. Compared with survivors, decedents were older, diabetic, had extant CAD, and were more likely to present with CLI as their indication for bypass surgery, P<.05. After adjustment for the above, clinical chemistry and inflammatory parameters significant for all cause mortality were albumin, HR .43 (95% CI .26–.71); P=.001, estimated glomerular filtration rate (eGFR), HR .98 (95% CI .97–.99), P=.023, high sensitivity C-reactive protein (hsCRP), HR 3.21 (95% CI 1.21–8.55), P=.019, and soluble vascular cell adhesion molecule (sVCAM), HR 1.74 (1.04–2.91), P=.034. Of all inflammatory molecules investigated, hsCRP proved most robust and representative of the integrated inflammatory response. Albumin, eGFR, and hsCRP improved the c-statistic and IDI beyond that of the clinical model and produced a final c-statistic of .82. Conclusions A risk prediction model including traditional risk factors and parameters of inflammation, renal function and nutrition had excellent discriminatory ability in predicting all cause mortality in patients with clinically advanced PAD undergoing bypass surgery.

Risk factors for major leg amputation in patients treated endovascularly due to critical limb ischaemia

“…2). However, this effect was relatively weak (HR 0.97), which, in our opinion, supports the hypothesis that a low cholesterol level in patients with a leg amputation should be recognized, not as an atherosclerosis risk factor, but as a marker of the general severity of a patient's malnutrition status [27]. We also found a strong effect of female gender (HR of about 12), blood creatinine (HR of about 7), and smoking habit (HR of about 4) on the risk of leg amputation (Tab.…”

Medical Management of Peripheral Arterial Disease

“…22 These results are relevant because a recent prospective cohort study of 225 patients undergoing lower-extremity bypass had a mean LDL of 63.7 mg/dL (60.9 mg/dL for those on statin therapy and 74.9 for those not on statin therapy at the time of surgery). 23 Thus, a good number of these advanced PAD patients had LDL levels within current guidelines, even without being on a statin at the time of their leg surgery. Yet, in the same cohort, high-sensitivity C-reactive protein levels were notably elevated, with a mean value of 12.0 mg/L (median, 3.0 mg/L).…”

Association between n-3 polyunsaturated fatty acid content of red blood cells and inflammatory biomarkers in patients with peripheral artery disease

“…In addition, we used the Kruskal-Wallis test to evaluate differences in CRP levels across the three omega-3 index categories proposed by Harris et al (defined as <4%, 4%–8%, >8%, corresponding to high, intermediate, and low CAD risk, respectively 21 ). Finally, having previously shown that patients with PAD and elevated CRP values have adverse cardiovascular and re-vascularization outcomes 23,40 , we used both unadjusted and fully adjusted logistic models to estimate the association of the omega-3 index with an elevated CRP (>5 mg/dL). Statistical analyses were performed using Stata/SE 12 (StataCorp, College Station, TX).…”

“…In patients with stable CAD, the omega-3 index has been inversely associated with inflammation as measured with CRP. 22 It is important to understand whether this relationship exists in patients with PAD as well, as inflammation appears to be more severe in these patients and correlates with poorer outcomes 7–10,23 . The goal of this study was to determine if the omega-3 index is associated with circulating markers of inflammation and endothelial function in patients with PAD.…”