Carsten Thilo Herz

Center-based patient care enhances survival of elderly patients suffering from peripheral arterial disease.

Abstract Objectives: Recent advances in catheter-based intervention in patients with symptomatic peripheral arterial disease (PAD) have halved mortality. Mortality of PAD patients still remains high compared to other clinical forms of atherosclerosis. Intensified patient care might increase adherence to medical management and benefit the survival of PAD patients. Methods: Two patient cohorts were compared in a longitudinal prospective follow-up study. 370 PAD patients were included in the intensified center-based vascular medicine group (VMC group) and 332 PAD patients were treated by their usual primary care physician (PCP group). Survival in both groups was compared by Kaplan–Meier and Cox-regression analyses after 5 years. Results: Survival of patients in the VMC group was 90.8% compared to 66% in the PCP group. Thus, survival was improved by 24.9% by center-based care (absolute risk CI: 19–30.7%; 38% relative risk). PCP treatment increased all-cause mortality by a hazard ratio of 3.7 (95% CI: 2.5–5.5; p < .001). Mortality in the VMC group was significantly associated with the non-modifiable risk factors age, C-reactive protein, and nephropathy in multivariable analyses. Conclusion: These data imply that multi-morbid elderly PAD patients still benefit by intensified specialist care compared to the usual primary care setting. KEY MESSAGES Center-based patient care improves survival in patients with peripheral arterial disease; mortality was reduced from 82 to 21 events per 1000 patient-years (rate ratio 0.26). Mortality was related to age (HR 1.46), CRP (HR 1.36), and nephropathy (HR 2.7). A multifactorial approach combining adequate drug prescription, accomplishment of agreed goals and repetitive training to initiate, implement, and persist treatment adaptations was applied.

Angiopoietin-2 and Survival in Peripheral Artery Disease Patients

Survival of peripheral arterial disease (PAD) patients increased over the last decade due to increased use of secondary preventive medication and rapid revascularization of PAD patients. Angiogenetic markers such as vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and its receptor Tie-2 might be useful markers to assess the residual risk for mortality in PAD patients. The aim of this study was to evaluate angiogenetic markers for the prediction of mortality in a PAD cohort. For this purpose, 366 patients (mean age: 69 ± 10 years) with PAD Fontaine stage I or II were included and followed up over a 5-year study period. Serum Ang-2, Tie-2 and VEGF levels were measured by bead-based multiplex assay. All-cause mortality and major cardiovascular events (MACE) including all-cause death, non-fatal stroke and non-fatal myocardial infarction were analysed by Kaplan-Meier and Cox regression analyses after 5 years. Ang-2 was associated with Tie-2 (R = 0.151, p = 0.006) and VEGF levels (R = 0.160, p = 0.002). However, only Ang-2 was linked to all all-cause mortality in PAD patients (hazard ratio [HR]: 1.55 [1.23-2.15], p = 0.008) even after adjustment for age and gender, haemoglobin A1c, low-density lipoprotein cholesterol, systolic blood pressure and glomerular filtration rate (HR: 1.44 [1.03-2.00], p = 0.032). Furthermore, an association of Ang-2 and MACE in PAD patients (HR: 1.36 (1.03-1.78), p = 0.028) was found. This result implies that Ang-2 might be used as an additional marker to stratify PAD patients to predict poor mid-term life expectancy.

FABP4 and Cardiovascular Events in Peripheral Arterial Disease

Fatty acid–binding protein 4 (FABP4) is a possible biomarker of atherosclerosis. We evaluated FABP4 levels, for the first time, in patients with peripheral artery disease (PAD) and the possible association between baseline FABP4 levels and cardiovascular events over time. Patients (n = 327; mean age 69 ± 10 years) with stable PAD were enrolled in this study. Serum FABP4 was measured by bead-based multiplex assay. Cardiovascular events were analyzed by FABP4 tertiles using Kaplan-Meier and Cox regression analyses after 5 years. Serum FABP4 levels showed a significant association with the classical 3-point major adverse cardiovascular event (MACE) end point (including death, nonlethal myocardial infarction, or nonfatal stroke) in patients with PAD (P = .038). A standard deviation increase of FABP4 resulted in a hazard ratio (HR) of 1.33 (95% confidence interval [95% CI]: 1.03-1.71) for MACE. This association increased (HR: 1.47, 95% CI: 1.03-1.71) after multivariable adjustment (P = .020). Additionally, in multivariable linear regression analysis, FABP4 was linked to estimated glomerular filtration rate (P < .001), gender (P = .005), fasting triglycerides (P = .048), and body mass index (P < .001). Circulating FABP4 may be a useful additional biomarker to evaluate patients with stable PAD at risk of major cardiovascular complications.