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.

Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based cohorts: results from the KORA studies.

BACKGROUND: Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and antioxidative glycoprotein. Plasma apoA-IV levels are elevated in patients with primary chronic kidney disease (CKD) or renal failure. The association between apoA-IV and kidney function has not been investigated in the general population; therefore, we analysed this relationship in two large population-based cohorts. METHODS: Plasma apoA-IV concentrations were measured in the Cooperative Health Research in the Region of Augsburg (KORA) F3 (n = 3159) and KORA F4 (n = 3061) studies. CKD was defined by the serum creatinine-estimated glomerular filtration rate (eGFR) and/or urine albumin-to-creatinine ratio. RESULTS: Mean (±SD) apoA-IV concentration was 17.3 ± 4.7 mg dL(-1) in KORA F3 and 15.3 ± 4.3 mg dL(-1) in KORA F4. Fully adjusted linear mixed models revealed a significant association between apoA-IV concentration and lower eGFR in the third and fourth versus the first quartile of apoA-IV (ß = -1.78 mL min(-1) /1.73 m², P = 0.0003 and ß = -5.09 mL min(-1) /1.73 m², P = 2.83 × 10(-23) , respectively). ApoA-IV was significantly associated with an eGFR of <60 mL min(-1) /1.73 m², which was observed in 601 of the 6220 study participants [odds ratio (OR) 1.46, P = 0.03 and OR 3.47, P = 6.84 × 10(-15) for the third and fourth vs. the first quartile of apoA-IV, respectively]. Adding apoA-IV (fourth vs. first quartile) to the fully adjusted model significantly improved discrimination of eGFR <60 mL min(-1) /1.73 m² in KORA F3 [integrated discrimination improvement (IDI) 0.03, P = 1.30 × 10(-7) ] and KORA F4 (IDI 0.04, P = 1.32 × 10(-9) ) beyond classical risk factors for CKD. CONCLUSION: The present analysis in two population-based cohorts revealed that high plasma apoA-IV concentrations are strongly associated with low kidney function defined by eGFR independent of major CKD risk factors. ApoA-IV appears to be an early marker of impaired kidney function.

Content validation of the international classification of functioning, disability and health core set for stroke from gender perspective using a qualitative approach.

BACKGROUND: The extended ICF Core Set for stroke is an application of the International Classification of Functioning, Disability and Health (ICF) of the World Health Organisation (WHO) with the purpose to represent the typical spectrum of functioning of persons with stroke. AIM: The objective of the study is to add evidence to the content validity of the extended ICF Core Set for stroke from persons after stroke taking into account gender perspective. DESIGN AND SETTING: A qualitative study design was conducted by using individual interviews with women and men after stroke in an in- and outpatient rehabilitation setting. METHODS: The sampling followed the maximum variation strategy. Sample size was determined by saturation. Concepts from qualitative data analysis were linked to ICF categories and compared to the extended ICF Core Set for stroke. RESULTS: Twelve women and 12 men participated in 24 individual interviews. In total, 143 out of 166 ICF categories included in the extended ICF Core Set for stroke were confirmed (women: N.=13; men: N.=17; both genders: N.=113). Thirty-eight additional categories that are not yet included in the extended ICF Core Set for stroke were raised by women and men. CONCLUSION: This study confirms that the experience of functioning and disability after stroke shows communalities and differences for women and men. The validity of the extended ICF Core Set for stroke could be mostly confirmed, since it does not only include those areas of functioning and disability relevant to both genders but also those exclusively relevant to either women or men. CLINICAL REHABILITATION IMPACT: Further research is needed on ICF categories not yet included in the extended ICF Core Set for stroke.

Apolipoprotein A-IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus--a post hoc analysis of the 4D Study.

BACKGROUND: Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apoA-IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. METHODS: This post hoc analysis was performed in the German Diabetes Dialysis Study (4D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apoA-IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index (BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. RESULTS: Mean (±SD) apoA-IV concentration was 49.8 ± 14.2 mg dL(-1). Age- and gender-adjusted apoA-IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL(-1) increase; P < 0.001). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio (HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m(-2) (HR = 0.87, 95% CI 0.82-0.94, P < 0.001) and those in the nonwasting group according to the extended definition (HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apoA-IV at baseline. Further associations were observed for sudden cardiac death. ApoA-IV was less strongly associated with atherogenic events such as myocardial infarction. CONCLUSIONS: Low apoA-IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status.

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.

Gender-specific association of adiponectin as a predictor of progression of chronic kidney disease: the Mild to Moderate Kidney Disease Study.

Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adiponectin for the progression of CKD in patients enrolled in the Mild to Moderate Kidney Disease Study. The primary end point was defined as a doubling of the baseline serum creatinine and/or terminal renal failure in 177 patients who completed a prospective follow-up of 7 years. Patients who reached a progression endpoint (n=65) were significantly older, had higher baseline serum creatinine, proteinuria and adiponectin concentrations and more components of the metabolic syndrome. A gender-stratified Cox model revealed adiponectin in men as a significant predictor of progression after adjustment for age, glomerular filtration rate, and proteinuria. Male patients with adiponectin levels above their ROC analysis-derived optimal cutoff of 4 microg/ml had a significantly faster progression than patients below this point. This prospective long-term study in patients with CKD indicates high adiponectin as a novel independent predictor of disease progression in men but not in women. Our observation may be relevant for other conditions of progressive vascular sclerosis and diabetic nephropathy.

Content comparison of health-related quality of life measures used in stroke based on the international classification of functioning, disability and health (ICF): a systematic review.

OBJECTIVE: To examine and compare the contents of health-related quality of life (HRQoL) measures used in stroke, based on the ICF as the frame of reference. DESIGN: We conducted a systematic literature review to select current generic and condition-specific HRQoL measures applied in stroke. We examined the contents of the selected measures by linking the concepts within the instruments' items to the ICF. RESULTS: The systematic literature review resulted in the selection of six generic and seven stroke-specific HRQoL measures. Within the selected instruments we identified 979 concepts. To map these concepts, we used 200 different ICF categories. None of the ICF categories is contained in all of the instruments. The most frequently used category is 'b152 Emotional functions' contained in 53 items from 10 instruments. Stroke-specific measures more often address 'Mental functions', while the selected generic instruments more often include Environmental Factors. DISCUSSION: The present study provides an overview on current HRQoL measures in stroke with respect to their covered contents and provides valuable information to facilitate the selection of appropriate instruments for specific purposes in clinical as well as research settings.

A simple score predicts future cardiovascular events in an inception cohort of dialysis patients.

Vascular calcifications are very common in dialysis patients and have been shown to be associated independently with outcome. However, all of these studies used prevalent patients on dialysis since many years. We investigated vascular calcifications in an inception cohort of dialysis patients and followed them for cardiovascular disease outcomes during an average observation period of 66 months. One hundred and fifty-four Caucasian dialysis patients were enrolled in one Austrian dialysis center. Standardized plain radiographs from the pelvis and calves were carried out in all patients at the start of dialysis therapy. Vascular calcifications were assessed by a single radiologist. At the start of renal replacement therapy, 67.5% of the patients showed vascular calcifications. During follow-up, 29.9% of patients suffered a cardiovascular event. An additive 'vascular risk score', constructed from the presence of vascular calcifications and/or previous cardiovascular events before the start of dialysis treatment, showed the strongest independent association with cardiovascular events in the Cox regression model adjusted for various risk factors. The presence of each of these two conditions was associated with a hazard ratio of 2.03 (95% confidence interval 1.19-3.46) and a hazard ratio twice as high if both conditions were present. In summary, vascular calcifications on plain X-rays of pelvis and calves are largely present in incident dialysis patients. A history of a cardiovascular event in the predialysis period together with vascular calcifications at the beginning of dialysis therapy is a more powerful predictor of a cardiovascular event than age, smoking, diabetes, or other traditional risk factors.