Lipoprotein apheresis in patients with peripheral artery disease and lipoprotein(a)-hyperlipoproteinemia: 2-year follow-up of a prospective single center study.

OBJECTIVE: Elevated plasma levels of lipoprotein(a) [Lp(a)], referred to as lipoprotein(a)-hyperlipoproteinemia [Lp(a)-HLP], are an independent risk factor for atherosclerosis. Lipoprotein apheresis (LA) enables an effective reduction of Lp(a) plasma levels. The present study investigates the effects of LA in patients with Lp(a)-HLP and peripheral artery disease (PAD). METHODS: Ten patients with isolated Lp(a)-HLP and severe PAD and who had recently undergone a revascularization (index procedure) were prospectively included in this observational single center study. All patients received weekly LA. Ankle-brachial-index (ABI), transcutaneous partial oxygen pressure (tcpO2), pain level, and walking distance were assessed at baseline and at the follow ups scheduled 1, 3, 6, 12, and 24 months after initiation of LA. The number of revascularizations within 12 months prior and within 24 months after the index procedure was determined. RESULTS: As early as 1 month after initiation of LA, all investigated parameters had improved significantly compared to baseline. This improvement was further substantiated under LA throughout the entire follow-up period. Comparing baseline results with the 24-month follow-up, the average ABI increased from 0.53 ± 0.15 to 0.97 ± 0.08 (P < 0.001). The mean tcpO2 also increased from 42.9 ± 2.3 mmHg to 61 ± 4.6 mmHg (P < 0.001). The improved perfusion led to a reduction of the mean pain level from 7.0 ± 1.5 to 1.1 ± 0.4 (P < 0.001) on a visual analogue scale (VAS) and an extension of the mean walking distance from 87 ± 60 m to 402 ± 119 m (P < 0.001). All patients suffered from severe PAD with a high number of revascularizations in the 12 months prior to the index procedure (35 procedures in 120 patient-months). Since initiation of LA, the number of revascularizations dropped significantly and remained very low during the entire follow-up period (2 procedures in 229 patient-months, P < 0.001). CONCLUSION: In patients with Lp(a)-HLP and severe PAD, LA results in sustained improvement of circulation, pain level and walking distance. The number of repeat revascularizations is strongly reduced under LA treatment.

Screening of COPD patients for abdominal aortic aneurysm.

PURPOSE: Screening for abdominal aortic aneurysm (AAA) in "men aged over 65 years who have ever smoked" is a recommended policy. To reduce the number of screenings, it may be of value to define subgroups with a higher prevalence of AAA. Since chronic obstructive pulmonary disease (COPD) and AAA are associated with several common risk factors, this study investigates the prevalence of AAA in COPD patients. PATIENTS AND METHODS: Patients with COPD were identified via the hospital information system. Inclusion criteria were: COPD stage I-IV, ability to give full consent, and age >18 years; exclusion criteria were: patient too obese for an ultrasound check, previously diagnosed AAA, prior surgery for AAA, or ethical grounds such as concomitant advanced malignant or end-stage disease. The primary endpoint of the study was an aortic diameter measured by ultrasound of ≥30 mm. Defined secondary endpoints were evaluated on the basis of medical records and interviews. RESULTS: Of the 1,180 identified COPD patients, 589 were included in this prospective study. In 22 patients (3.70%), the aortic diameter was ≥30 mm, representing an AAA prevalence of 6.72% among males aged >65 years. The risk of AAA increased with the following comorbidities/risk factors: male sex (odds ratio [OR] 2.98), coronary heart disease (OR 2.81), peripheral arterial occlusive disease (OR 2.47), hyperlipoproteinemia (OR 2.77), AAA in the family history (OR 3.95), and COPD stage I/II versus IV (OR 1.81). CONCLUSION: The overall AAA prevalence of 3.7% in our group of COPD patients is similar to that of the general population aged >65 years. However, the frequency of AAA in male COPD patients aged >65 years is considerably higher (6.72%) and increased further still in those individuals with additional comorbidities/risk factors. Defining subgroups with a higher risk of AAA may increase the efficiency of screening.

Lipoprotein apheresis in patients with peripheral artery disease and hyperlipoproteinemia(a).

OBJECTIVE: Hyperlipoproteinemia(a) [Lp(a)-HLP] is a major risk factor for severe atherosclerosis. The present investigation sought to assess the effect of lipoprotein apheresis (LA) in patients with peripheral artery disease (PAD) and Lp(a)-HLP. METHODS: In January 2013, we started a registry for Lp(a)-HLP patients who receive weekly LA in our center. So far, ten patients with severe PAD and isolated Lp(a)-HLP who recently underwent revascularization (index procedure) have been included. Pain level, ankle-brachial-index (ABI), transcutaneous oxygen pressure (tcpO2) and walking distance were determined before, as well as 1, 3, 6 and 12 months after initiation of LA. Furthermore, the mean time interval between revascularizations within the 12 months prior to the index procedure and up to 12 months after the index procedure was assessed. RESULTS: All analyzed parameters significantly improved under LA. When comparing the results before LA with the results after 12 months, the ankle-brachial-index increased from 0.5 ± 0.2 to 0.9 ± 0.1 (P < 0.001). The tcpO2 levels also increased from 42.9 ± 2.3 mmHg to 59.0 ± 8.9 mmHg (P < 0.001). The improved microcirculation was associated with a reduction of the mean pain level from 7.0 ± 1.5 to 2.0 ± 0.8 (P < 0.001) as determined using the visual analog scale. The walking distance increased from 87 ± 60 m to 313 ± 145 m (P < 0.001). Importantly, the frequency of revascularization procedures was strongly decreased under LA. All patients combined underwent 35 revascularizations within the 12 months prior to the index procedure (mean interval between two revascularizations: 104.3 days). Since the index procedure, only one revascularization was necessary within 79 patient-months under LA (mean interval: 2404.5 days, P < 0.001). CONCLUSION: LA improves circulation, oxygen supply, level of pain and walking distance in patients with severe PAD and Lp(a)-HLP. The frequency of revascularization procedures is strongly reduced under LA treatment.

Circulating angiogenic factors in patients with thromboangiitis obliterans.

BACKGROUND: Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO. METHODOLOGY/PRINCIPAL FINDINGS: TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group) were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dim)CD34(+) progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dim)CD34(+) progenitor cells co-expressing VEGF receptor-2 (VEGFR2) was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA) of common angiogenic factors (such as VEGF) did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay) and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs). Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients. CONCLUSION: Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation) on endothelial cells, which may contribute to vascular pathology in this patient population.

Successful treatment of thromboangiitis obliterans (Buerger's disease) with immunoadsorption: results of a pilot study.

BACKGROUND: No established therapy is available for patients with thromboangiitis obliterans (TAO) and critical limb ischemia. Since abnormalities of the immune system appear to be involved in the pathogenesis, we investigated in this pilot study the efficiency of Ig immunoadsorption (IA) therapy. METHODS: Ten patients with advanced TAO underwent a single IA course over five consecutive days. Before IA angiography was performed. In addition, the following were conducted prior to IA, directly after, as well as 1, 3, and 6 months after IA: clinical examination, pain scale (0-10), treadmill test for evaluation of maximum walking distances, and several angiological methods for evaluation of disease extent: photoplethysmography, ultrasound Doppler, and transcutaneous assessment of partial carbon dioxide (tcPCO(2)) and oxygen (tcPCO(2)) pressure. RESULTS: Immunoadsorption treatment was tolerated without side effects. Pain intensity decreased rapidly from 7.7 ± 0.8 (mean ± SEM) before treatment to 2.0 ± 1.2 at the second day of IA. One month after IA, all patients were without pain. This functional amelioration persisted over the follow-up period of 6 months. Correspondingly, maximum walking distances significantly increased from 301.7 ± 191.4 to 727.0 ± 192.7 m immediately after IA, and further continuously up to 1,811.0 ± 223.7 at 6 months after IA. Healing of ischemic ulcerations was observed in all patients during follow-up. (tcPCO(2)) and (tcPCO(2)) values as well as photopletysmographic data that were severely compromised before IA reflecting reduced tissue oxygenation and perfusion showed rapid amelioration reaching normal values at 1 month. CONCLUSION: Anti-Ig IA appears to be an effective therapeutic option for patients with advanced TAO.