Mitochondrial DNA copy number is associated with all-cause mortality and cardiovascular events in patients with peripheral arterial disease.

BACKGROUND: Dysfunctional mitochondria have an influence on inflammation and increased oxidative stress due to an excessive production of reactive oxygen species. The mitochondrial DNA copy number (mtDNA-CN) is a potential biomarker for mitochondrial dysfunction and has been associated with various diseases. However, results were partially contrasting which might have been caused by methodological difficulties to quantify mtDNA-CN. OBJECTIVE: We aimed to investigate whether mtDNA-CN is associated with peripheral arterial disease (PAD) as well as all-cause mortality and cardiovascular events during seven years of follow-up. METHODS: A total of 236 male patients with PAD from the Cardiovascular Disease in Intermittent Claudication (CAVASIC) study were compared with 249 age- and diabetes-matched controls. MtDNA-CN was measured with a well-standardized plasmid-normalized quantitative PCR-based assay determining the ratio between mtDNA-CN and nuclear DNA. RESULTS: Individuals in the lowest quartile of mtDNA-CN had a twofold increased risk for PAD which, however, was no longer significant after adjusting for leukocytes and platelets. About 67 of the 236 patients had already experienced a cardiovascular event at baseline and those in the lowest mtDNA-CN quartile had a 2.34-fold increased risk for these events (95% CI 1.08-5.13). During follow-up, 37 PAD patients died and 66 patients experienced a cardiovascular event. Patients in the lowest mtDNA-CN quartile had hazard ratios of 2.66 (95% CI 1.27-5.58) for all-cause-mortality and 1.82 (95% CI 1.02-3.27) for cardiovascular events compared with the combined quartile 2-4 (adjusted for age, smoking, CRP, diabetes, prevalent cardiovascular disease, leukocytes and platelets). CONCLUSION: This investigation supports the hypothesis of mitochondrial dysfunction in peripheral arterial disease and shows an association of low mtDNA-CNs with all-cause-mortality and prevalent and incident cardiovascular disease in PAD patients with intermittent claudication.

How safe are carotid endarterectomy and carotid artery stenting in the early period after carotid-related cerebral ischemia?

Timing of treatment in carotid artery disease is still a matter of debate. So far there is controversial literature available concerning the safety of rapid treatment after a qualifying neurological event. Carotid endarterectomy turned out to be more effective in stroke prevention when carried out closer after the onset of symptoms. The initial "two weeks" cut off for surgery meanwhile turned into a "as soon as possible" treatment policy. In case of a cerebral infarction it seems reasonable, however, to delay surgery. Less evidence exists about the ideal timing of carotid artery stenting. Data analysis from the Carotid Stenosis Trialists' Collaboration showed that the early days after plaque rupture carry a high risk for periprocedural complications after carotid artery stenting. The analysis of a large register series showed, that carotid artery stenting carried a significantly higher risk for complications in patients with and without cerebral infarction when performed within 48 hours after the onset of symptoms.

Very urgent carotid endarterectomy does not increase the procedural risk.

OBJECTIVES: The timing of CEA for symptomatic internal carotid artery (ICA) stenosis remains a matter of controversy. Recent registry data showed a significantly increased risk, especially in the very early days after the onset of symptoms. In this study the outcome of CEA in the hyperacute phase has been investigated. METHODS: The outcome of CEA for symptomatic ICA stenosis between January 2004 and December 2013 has been retrospectively analyzed. Patients were divided into four timing groups: surgery within 0 and 2 days, between 3 and 7 days, 8 and 14 days, and thereafter. The post-operative 30 day stroke and death rates were assessed. RESULTS: A total of 761 symptomatic patients (40.1% with transient ischemic attack [TIA], 21.3% with amaurosis fugax, and 38.6% with ischemic stroke) were included, with an overall peri-operative stroke and death rate of 3.3%. A stroke and death rate of 4.4% (9/206) for surgery within 0 and 2 days, 1.8% (4/219) between 3 and 7 days, 4.4% (6/136) between 8 and 14 days, and 2.5% (5/200) in the period thereafter (p = .25 for the difference between the groups) was observed. The timing of surgery did not influence the peri-operative outcome in a multivariate regression analysis (OR 0.93 [0.63-1.36], p = .71). CONCLUSIONS: These data show that very urgent surgery in symptomatic patients can be performed without increased procedural risk. Given the fact that ruptured plaques with neurological symptoms carry the highest risk of a recurrent ischemic event in the first 2 days, treating patients as soon as possible to offer the highest benefit in stroke prevention is recommended.

Carotid endarterectomy within seven days after the neurological index event is safe and effective in stroke prevention.

BACKGROUND: Timing of surgery remains a controversial subject with some concerns persisting that the benefit of early carotid endarterectomy (CEA) offsets the perioperative risks. We investigated the neurological outcome of patients with symptomatic internal carotid artery (ICA) stenosis after surgery in relation to the timing of treatment. METHODS: From January 2005 to June 2010, 468 patients (n = 349 male, 74.6%, median age 71 years) underwent CEA for symptomatic stenosis. Perioperative morbidity and mortality rates were assessed in the 30 days' follow-up. RESULTS: The median time interval between index event and CEA was 7 days; the overall stroke and death rate reached 3.4%. There was no difference in the 30 days' rate of stroke /death rate, depending on the timing of surgery (n = 5/241, 2.1% in patients treated within 1 week vs. n = 10/215, 4.7% in patients treated thereafter, p = 0.12). Patients with a postoperative neurological deterioration had more often an ischaemic infarction on preoperative cerebral computed tomography (CCT) compared with those without deterioration (n = 6/15, 40.0% vs. n = 39/441, 9.0%, p = 0.003). Logistic regression analysis showed that patients with preoperative infarction on CCT had the highest risk for postoperative neurological deterioration. CONCLUSION: An infarction on the preoperative CCT leads to an increased risk for a postoperative deterioration after CEA. Patients should be treated at an early point in time with bland CCTs.

Successful treatment of a patient with a severely calcified aorta by an ascending aorta to iliac artery graft--a case report.

Coral reef aorta is a rare, unique entity with extensive calcification of the entire aorta, mainly the supra- and juxtarenal part. The main symptoms are lower limb claudication, hypertension, deterioration of renal function and angina abdominalis. We report a case of successful treatment of a patient with a coral reef aorta by an ascending aorta to iliac artery bypass graft. Five years later the descending aorta was found to be completely occluded with visceral and distal perfusion via the bypass only.

Ankle-brachial index and peripheral arterial disease.

Patients with peripheral arterial disease including those with intermittent claudication have a high risk for cardiovascular and cerebrovascular morbidity and mortality. The outcome of patients with intermittent claudication is less limited by local complications in the leg than by the systemic complications of coronary and cerebral vessels. About 30 % of these patients will die within 5 years, three-quarters of them due to vascular events. Analyses using data of the KORA Study 2004/2005 (F3), a follow-up examination of the participants of the MONICA Survey 1994/95 (S3), will try to identify biochemical as well as genetic risk factors for peripheral arterial disease. The anti-atherogenic apolipoprotein A-IV will be one of our candidates of interest.

Carotid endarterectomy after ischemic stroke--is there a justification for delayed surgery?

PURPOSE: To assess the relationship between outcome of carotid surgery and wait after ischemic stroke. METHODS: We retrospectively analysed data from patients undergoing carotid endarterectomy after ischemic stroke. We investigated the time interval between the event and endarterectomy in relation to surgical results and complications. RESULTS: Between January 2000 and December 2003, 104 patients were scheduled to undergo carotid endarterectomy after a recent stroke. Endarterectomy was performed within 6 h in seven patients (6.7%); within 4 weeks in 29 (27.9%); 4 weeks or more in 62 (59.6%) and six (5.8%) patients received no further therapy. Perioperative complications among patients treated within 4 weeks were 3.4% and were comparable to those treated after 4 weeks (4.8%). However, more than 12% of the patients awaiting operation experienced a new cerebrovascular event (ischemic stroke or carotid occlusion), most of them occurred in the 3rd or 4th week after the initial event. CONCLUSION: Our data indicates, that carotid endarterectomy can be performed with a comparable risk within a short delay after stroke. In addition severe cerebrovascular events occurring within the waiting period may be avoided.

Neuropathic pain after femoropopliteal bypass surgery.

OBJECTIVE: This retrospective study was performed to investigate prolonged postoperative pain in the area of the proximal or distal scar or the bypass tunnel after femoropopliteal bypass surgery to treat symptomatic peripheral arterial disease. PATIENTS AND METHODS: Ninety-three patients with peripheral arterial disease who underwent femoropopliteal bypass surgery between January 2000 and December 2002 were included in the study. The short-form McGill Pain Questionnaire was used to score pain. Ultrasound examination of the soft tissue around the graft was performed to exclude other pathologic conditions responsible for pain, such as inflammatory processes, perigraft reactions, swollen lymph nodes, and hematomas. RESULTS: Pain in at least one scar existed in 22 patients on average 13.9 +/- 9.8 months after surgery. In 10 patients pain existed simultaneously along the inguinal scar and the above-knee or below-knee scar. Pain along the bypass tunnel was experienced by seven patients. Most patients had mild to moderate pain. The mean numeric ranking score of pain severity in patients with pain was 4.2 +/- 2.3. The occurrence of prolonged postoperative pain was not associated with age, gender, diabetes, indication for surgery, material or type of bypass, number of preceding operations, or postoperative wound complications. Only follow-up time after femoropopliteal bypass surgery tended to be lower in patients with pain compared with those without pain. CONCLUSION: Prolonged postoperative neuropathic pain along the distal and proximal incision or the bypass tunnel exists in one fourth of patients after femoropopliteal bypass surgery. Patients should be informed of this kind of complication before surgery. The results of our study justify further investigations of the origin and treatment of this pain, to find effective methods to reduce the incidence of prolonged postoperative pain after femoropopliteal bypass surgery.