Undetected Peripheral Arterial Disease Among Older Adults With Alzheimer's Disease and Other Dementias.

BACKGROUND: Peripheral arterial disease (PAD) was reported to increase the risk of dementia(s) even more than stroke. We assessed the prevalence of PAD in a group with definite diagnosis of dementia. METHODS: Patients aged 65 years or older with Alzheimer's disease (AD), vascular dementia (VaD), or AD-VaD were enrolled (n = 162, mean age: 78.87 [6.05] years). An age- and gender-matched control group was also included (n = 190). Peripheral arterial disease was diagnosed by the ankle-brachial index. RESULTS: Frequency of PAD among patients with and without dementia was 35.2% and 16.3%, respectively ( P < .001), being similar among different types of dementia. After adjustment for covariates, dementia (odds ratio: 2.41, 95% confidence interval: 1.34-4.32; P = .003) was among the predictors of PAD diagnosis along with older age, female gender, and diabetes. CONCLUSIONS: The prevalence of PAD was more than double in patients with dementia, with no difference among AD, VaD, and AD-VaD types.

The association of profilin-1 levels with survival in chronic kidney disease.

BACKGROUND: Profilin-1 is a ubiquitous, actin-binding protein that plays an important role in the regulation of actin polymerization and cytoskeleton remodelling and contributes to vascular dysfunction. We conducted this study to investigate the association of serum profilin-1 levels with fatal and nonfatal CVE in a cohort of patients with stage 1-5 CKD. MATERIALS AND METHODS: Serum concentrations of profilin-1 levels were determined by enzyme-linked immunosorbent assay. Endothelium-dependent vasodilatation (flow-mediated dilatation [FMD]) and endothelium-independent vasodilatation (nitroglycerine-mediated dilatation [NMD]) of the brachial artery were assessed noninvasively, using high-resolution ultrasound. RESULTS: Both fatal and nonfatal CVE were significantly higher in patients with high profilin-1 levels. Kaplan-Meier survival curves showed that patients with profilin-1 below the median value (114 pg/mL) had higher cumulative survival compared with patients who had profilin-1 levels above the median value (log-rank test, P < .001). CONCLUSIONS: This is the first study that demonstrates the serum profilin-1 is independently associated with endothelial dysfunction, cardiovascular events and survival in patients with CKD.

IL-33 and ST2 levels in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events, and survival.

OBJECTIVE: Increased inflammation, associated with the increase in chronic kidney disease (CKD) stage, has a very important influence in vascular injury and cardiovascular diseases. In this study, we aimed to investigate the levels of IL-33 and ST2 in the different stages of CKD and to determine their effect on vascular damage and cardiovascular events (CVE). METHODS: This was an observational cohort study in which serum IL-33 and ST2 were obtained from 238 CKD (stages 1-5) patients. We examined the changes in IL-33/ST2 levels in CKD patients, as well as the association with a surrogate of endothelial dysfunction. Fatal and non-fatal CVE were recorded for a mean of 24 months. We also performed a COX regression analysis to determine the association of IL-33/ST2 levels with CVE and survival. RESULTS: IL-33 and ST2 levels were significantly increased and estimated glomerular filtration rates (eGFR) were decreased. Flow-mediated dilatation (FMD) was significantly decreased from stage 1 to stage 5 CKD. IL-33 and ST2 levels were associated with FMD, and ST2 was a predictor. Multivariate Cox analysis showed that the presence of diabetes mellitus, smoking, and proteinuria and haemoglobin, Hs-CRP, IL-33, and ST2 were associated with the risk of CVE. Kaplan-Meier survival curves showed that patients with IL-33 and ST2 levels below the median value (IL-33 = 132.6 ng/L, ST2 = 382.9 pg/mL) had a higher cumulative survival compared with patients who had IL-33 and ST2 levels above the median value (log-rank test, p = 0.000). CONCLUSION: This is the first study that demonstrates that serum IL-33 and ST2 are associated with vascular injury, cardiovascular events, and survival in CKD patients.

Thyroid function and cardiovascular events in chronic kidney disease patients.

BACKGROUND AND AIMS: Abnormalities of thyroid function are commonly seen in chronic kidney disease (CKD) patients. They are associated with adverse clinical conditions such as atherosclerosis, endothelial dysfunction, inflammation and abnormal blood pressure variability. We investigated the association between thyroid disorders and endothelial function, assessed by flow-mediated dilatation (FMD) and carotid intima-media thickness (CIMT), and cardiovascular events (CVE) in CKD patients. MATERIALS AND METHODS: This observational cohort study included 305 CKD (stages 1-5) patients. Routine biochemistry, including free T3, free T4 and thyroid stimulating hormone, fibroblast growth factor-23 (FGF-23) and FMD, CIMT were measured. We divided patients into four groups according to thyroid hormone status: euthyroidism, subclinical hyperthyroidism, subclinical hypothyroidism, and euthyroid sick syndrome. Fatal and composite CVE were recorded for a median 29 months. RESULTS: Patients with subclinical hypothyroidism had a higher prevalence of hypertension and diabetes and also were more likely to have higher values of systolic CIMT, phosphorus, intact parathormone (iPTH), FGF-23, homeostasis model assessment-insulin resistance and lower levels of FMD than euthyroid patients. In the unadjusted survival analysis, subclinical hypothyroidism and euthyroid sick syndrome were associated with an increased risk for the outcome as compared with euthyroidism [hazard ratio 30.63 (95 % confidence interval 12.27-76.48) and 12.17 (3.70-39.98), respectively]. The effects of subclinical hypothyroidism and euthyroid sick syndrome were maintained even in fully adjusted models. CONCLUSION: We demonstrated that subclinical hypothyroidism and euthyroid sick syndrome are associated with increased CVE in CKD patients. Further studies are needed to explore these issues.

Chitotriosidase as a novel biomarker of early atherosclerosis in hemodialysis patients.

INTRODUCTION: Increasing evidence suggests that inflammation and increased macrophage activity have a central role in pathogenesis of atherosclerosis. It is shown that chitotriosidase (CHIT-1) is a marker of macrophage activity in atherosclerotic plaque, and is found associated with severity of atherosclerotic lesion. There is no data about CHIT-1 activity of hemodialysis patients in the literature. Thus, we hypothesized that in hemodialysis patients, CHIT-1 levels might be a novel biomarker in early atherosclerosis. METHODS: Forty-five hemodialysis patients were included in the study (age: 61.93 ± 13.34). Intima media thickness (IMT) was evaluated with high-resolution B-mode ultrasonography. Biomarker levels were measured in serum of patients. FINDINGS: We found positive correlation among IMT, age (R: 0.426, P: 0.004) and, CHIT-1 value (R: 0.462, P: 0.001) in spearman correlation analysis. When age, CRP, creatinine, P, Alb, CHIT-1 were chosen as measures that can effect IMT in multiple regression model, IMT level was related with CHIT-1 (Beta: 0,396, P: 0.012) and age (Beta: 0,313 P: 0,048) independently. DISCUSSION: In conclusion, this is the first report showing that serum CHIT-1 level was related independently with carotid IMT in hemodialysis patients. This biomarker might have an unknown role in the development of atherosclerosis during uremia.

Endostatin in chronic kidney disease: Associations with inflammation, vascular abnormalities, cardiovascular events and survival.

BACKGROUND AND AIMS: Endostatin, generated from collagen XVIII, and endorepellin, possess dual activity as modifiers of both angiogenesis and endothelial cell autophagy. Plasma endostatin levels are elevated in a large number of diseases, and may reflect endothelial cell dysfunction. Few data on endostatins are available for patients with chronic kidney disease (CKD). We tested whether serum endostatin values are predictive for all-cause mortality and cardiovascular events (CVEs) in a CKD population. MATERIALS AND METHOD: A total of 519 CKD pre-dialysis patients were included. Baseline plasma endostatin levels were measured in all patients. All included patients were followed-up (time-to-event analysis) until occurrence of death, fatal or nonfatal CVEs. Fatal and nonfatal CVE including death, stroke, and myocardial infarction were recorded prospectively RESULTS: The mean age of the patients was 52.2±12.3years. There were 241 (46.4%) males, 111 (21.4%) had diabetes, 229 (44.1%) were smokers and 103 (19.8%) had a previous CVE. After a median follow-up of 46months, 46 patients died and 172 had a new CVE. In the univariable Cox survival analysis, higher endostatin levels were associated with a higher risk for both outcomes. However, after adjusting for traditional (age, gender, smoking status, diabetes, systolic blood pressure, HDL and total cholesterol) and renal-specific (eGFR, proteinuria and hsCRP) risk factors, endostatin levels remained associated only with the CVE outcome (HR=1.88, 95% CI 1.37-2.41 for a 1 SD increase in log endostatin values). CONCLUSION: Endostatin levels are independently associated with incident CVE in CKD patients, but show limited prediction abilities for all-cause mortality and CVE above traditional and renal-specific risk factors.

Relevance of uric acid and asymmetric dimethylarginine for modeling cardiovascular risk prediction in chronic kidney disease patients.

BACKGROUND: Both elevated serum uric acid and serum asymmetric dimethylarginine (ADMA) are risk factors for cardiovascular disease. We hypothesized that combined elevation of uric acid and ADMA amplifies the risk of all-cause mortality and/or cardiovascular events (CVE) in patients with chronic kidney disease (CKD). METHODS: A total of 259 patients with CKD stages 1-5 were followed up in a time-to-event analysis for all-cause mortality and fatal and non-fatal CVE (including death, stroke, and myocardial infarction). Baseline measurements included serum uric acid and ADMA and endothelial function [ultrasound determined flow-mediated dilatation (FMD)]. RESULTS: As a measure of endothelial function, log FMD value was positively associated with log eGFR, but negatively associated with log ADMA and log uric acid levels. During follow-up (median 38 months), 24 (9.3 %) deaths, 90 (34.7 %) CVE, and 95 (36.7 %) deaths and CVE (composite outcome) occurred. In the univariate Cox analysis, patients with both serum uric acid and ADMA levels above the median had an increased risk of all-cause mortality, CVE, and the composite outcome (HR 5.06, 95 % CI 2.01-12.76; HR 4.75, 95 % CI 2.98-7.59; and HR 4.13, 95 % CI 2.66-6.43, respectively). However, after adjustment for renal-specific risk factors (glomerular filtration rate, proteinuria, and hsCRP), this association was maintained only for CVE and the composite outcome. The addition of both biomarkers into a model with traditional and renal-specific risk factors did not increase the prediction abilities of the model for none of the three outcomes. CONCLUSION: Elevated serum uric acid and ADMA levels are associated with an increased cardiovascular risk, but their combination does not improve risk prediction. The effects are not additive, possibly because uric acid may lie in the causal pathway by which ADMA acts.

Osteoprotegerin in Chronic Kidney Disease: Associations with Vascular Damage and Cardiovascular Events.

Vascular injury and dysfunction contribute to cardiovascular disease, the leading cause of death in patients with chronic kidney disease (CKD). Osteoprotegerin (OPG) is a soluble member of the tumor necrosis factor receptor superfamily that has been linked to atherogenesis and endothelial dysfunction. Elevated circulating OPG levels predict future cardiovascular events (CVE). Our aim was to evaluate the determinants of circulating OPG levels, to investigate the relationship between OPG and markers of vascular damage and to test whether OPG improves risk stratification for future CVE beyond traditional and renal-specific risk factors in a CKD population. 291 patients with CKD stage 1-5 not on dialysis were included in the study. In the multivariate analysis, OPG was a significant predictor for flow-mediated dilatation, but not for carotid intima media thickness levels. During follow-up (median 36 months, IQR = 32-42 months), 87 patients had CVE. In the Cox survival analysis, OPG levels were independently associated with CVE even after adjustment for traditional and renal-specific cardiovascular risk factors. The addition of OPG to a model based on commonly used cardiovascular factors significantly improved the reclassification abilities of the model for predicting CVE. We show for the first time that OPG improves risk stratification for CVE in a non-dialysis CKD population, above and beyond a model with established traditional and renal-specific cardiovascular risk factors, including estimated glomerular filtration rate and fibroblast growth factor 23.

Ultrasonographic evaluation of the femoral cartilage thickness in patients with chronic renal failure.

OBJECTIVE: To investigate the effects of chronic renal failure (CRF) on the distal femoral cartilage thickness by using ultrasonography and to determine the relationship between cartilage thickness and certain disease-related parameters. DESIGN: Fifty-seven CRF patients (41 male and 16 female) (mean [SD] age, 44.7 [12.1] years) and 60 healthy controls (41 male and 19 female) (mean [SD] age, 43.5 [13.3] years) were enrolled in this study. Demographic and clinical characteristics were recorded. Cartilage thickness measurements were taken from the medial and lateral condyles, and intercondylar areas of both knees. RESULTS: Groups were similar in terms of age, weight, height, body mass index and gender (all p>0.05). The mean cartilage thickness was found to be less in CRF patients than in controls (statistically significant for medial condyles and intercondylar areas both in right and the left knees [all p<0.05]). Cartilage thickness showed no correlation with eGFR, and with the levels of serum urea, creatinine, calcium, magnesium, phosphor, hemoglobin, uric acid and as well as steroid use (all p>0.05) in CRF patients. CONCLUSION: In the light of our findings, we imply that patients with CRF have thinner femoral cartilage than healthy controls. This result may support the view that patients with CRF are at increased risk for developing early knee osteoarthritis. Last but not least, clinicians should be aware of the importance of rehabilitation strategies aimed at decreasing onset and progression of knee osteoarthritis in patients with CRF.

Individual variations in ankle brachial index measurement among Turkish adults.

PURPOSE: Variability of ankle brachial index (ABI) measured by the same observer in the same individual on three different occasions was examined. BASIC METHODS: A single morning ABI was initially determined (measurement 1) with handheld Doppler device. One to four weeks apart, another morning (measurement 2) and afternoon (measurement 3) ABI was measured on the same day. PRINCIPAL FINDINGS: A total of 161 adults were enrolled. Mean ABI was similar among the three measurements. ABI differed more than ≥0.15 in 15 individuals between measurement 1 and 3, in 10 subjects between measurement 1 and 2, and in 12 individuals between measurement 2 and 3. Intra-group correlation coefficients of reproducibility of ABI were 0.808 for single measurements (coefficient of the values lacking association with each other), and 0.927 for average measurements (coefficient of the values that were associated with each other). CONCLUSIONS: Although reproducibility of ABI values was found satisfactory, up to 12% of participants displayed more than 0.15 alternations between measurements, either on the same day or more than a week apart.

Effectiveness of the Stewart Method in the Evaluation of Blood Gas Parameters.

OBJECTIVES: In 1981, Peter A. Stewart published a paper describing his concept for employing Strong Ion Difference. In this study we compared the HCO3 levels and Anion Gap (AG) calculated using the classic method and the Stewart method. METHODS: Four hundred nine (409) arterial blood gases of 90 patients were collected retrospectively. Some were obtained from the same patients in different times and conditions. All blood samples were evaluated using the same device (ABL 800 Blood Gas Analyzer). HCO3 level and AG were calculated using the Stewart method via the website AcidBase.org. HCO3 levels, AG and strong ion difference (SID) were calculated using the Stewart method, incorporating the parameters of age, serum lactate, glucose, sodium, and pH, etc. RESULTS: According to classic method, the levels of HCO3 and AG were 22.4±7.2 mEq/L and 20.1±4.1 mEq/L respectively. According to Stewart method, the levels of HCO3 and AG were 22.6±7.4 and 19.9±4.5 mEq/L respectively. CONCLUSIONS: There was strong correlation between the classic method and the Stewart method for calculating HCO3 and AG. The Stewart method may be more effective in the evaluation of complex metabolic acidosis.

Systemic involvements and preferred treatments in a large cohort of Behçet's disease.

The immunosuppressive drugs are widely used in systemic involvements of Behçet's disease. This study is aimed to investigate the extent of clinical involvement and preferred treatment approaches for type of involvements in Behçet's patients from the whole country. All patients with the diagnosis of Behçet's disease were enrolled to the study. These patients analyzed whether they fulfill the International Study Group Criteria, and only those were further evaluated. Demographic and clinical characteristics, laboratory results and treatments ever used were recorded. Further analysis is done regarding clinical manifestations and preferred therapeutic approaches. A total of 863 patients with the diagnosis of Behçet's disease were detected, but 682 of them (female/male: 113/569) found to be appropriate for analysis. The remaining patients were included to the analysis. The frequencies of articular, ophthalmic and vascular involvement were 49, 43 and 21 %, respectively. Colchicine and corticosteroids were the most preferred agents. The immunosuppressive agents frequently used for organ involvements were azathioprine, cyclosporine A, interferon-α, sulphasalazine and cyclophosphamide with decreasing order of frequency. In this relatively young population composed from all over the country, the frequency of ophthalmologic, venous and neurological involvement is less frequent than previous reported cohorts. Azathioprine and cyclosporine were the drugs of choice as a chronic immunosuppressive agent in patients with organ involvement. The previously reported increased frequencies in other cohorts could be a result of the reference of severe patients to dedicated centers.

Abdominal obesity is associated with a lower ankle-brachial index in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) was linked to increased lifetime risk of cardiovascular disease. A low ankle-brachial index (ABI) is associated with accelerated atherosclerosis. The ABI value and the associated conditions in women with PCOS were searched in the present study. The ABI was measured using a handheld Doppler device and calculated using both standard and modified definitions. Women with PCOS (n = 103, mean age = 24.9 ± 5.9 years) had a mean ABI of 1.10 ± 0.10. A low ABI (≤0.9) was 2.9% and 14.6% using the standard and modified definitions, respectively. Mean ABI correlated negatively to body weight, BMI, waist circumference, waist-to-hip ratio, and hematocrit. Logistic regression analysis revealed higher waist-to-hip ratio as independently associated with a lower ABI. Frequency of ABI ≤0.9 in PCOS was lower than the general population. However, increased waist-to-hip ratio was a predictor of a lower ABI value.