Laser Doppler flowmetry evaluation of skin microvascular endothelial function in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MetS) is associated with high cardiovascular morbidity and mortality, and endothelial dysfunction is an early pathogenetic event in the MetS. Lifestyle changes and pharmacological intervention might partly restore endothelial function in MetS. Whereas an optimal non-invasive test for endothelial dysfunction is still being sought, the aim of this study was to assess the relationship between changes in skin microvascular endothelial function, detected by Laser Doppler flowmetry, and cardiovascular risk factors (CVRFs) of patients with MetS. DESIGN AND METHODS: 3081 patients (1865 women and 1216 men, mean age 53 ± 6 years) with MetS were enrolled in the study, which was conducted during the period of 2010-2014 at Vilnius University Hospital Santaros Klinikos. Skin microvascular endothelial function was evaluated using the Laser Doppler flowmetry in combination with the post-occlusive reactive hyperaemia test. The percentage change of flow from peak to the rest flow (PF-RF) was calculated and used as the main measure of endothelial function. RESULTS: The study showed that decrease in flow-mediated dilatation reflected by PF-RF was associated with increased triglycerides (p = 0.002), male sex (p < 0.001), and diabetes (p = 0.002). Patients with quite a few CVRFs (body mass index ≥25 kg/m2, smoking, diabetes, arterial hypertension, a positive history of dyslipidaemia) had significantly lower PF-RF score than patients only with one of these risk factors (p < 0.001). CONCLUSIONS: Changes in skin microvascular endothelial function are significantly associated with most CVRFs and depend on the number of CVRFs.

Inflammaging and Vascular Function in Metabolic Syndrome: The Role of Hyperuricemia.

Background and Objectives: Early vascular aging determines a more rapid course of age-related arterial changes. It may be induced by a proinflammatory state, caused by hyperuricemia and metabolic syndrome and their interrelationship. However, the impact of serum uric acid (SUA) on early arterial stiffening and vascular function remains uncertain. Materials and Methods: A total of 696 participants (439 women aged 50-65 and 257 men aged 40-55) from the Lithuanian High Cardiovascular Risk (LitHiR) primary prevention program were enrolled in the study. They underwent anthropometric measurements and laboratory testing along with arterial parameters' evaluation. Quality carotid stiffness (QCS), carotid-radial pulse wave velocity (crPWV), carotid-femoral pulse wave velocity (cfPWV), flow-mediated dilatation (FMD), and carotid intima-media thickness (CIMT) were registered. Results: We found that hyperuricemia was significantly associated with inflammation, registered by high-sensitivity C-reactive protein in both sexes. A very weak but significant association was observed between cfPWV and SUA in men and in women, while, after adjusting for risk factors, it remained significant only in women. A positive, weak, but significant association was also observed for QCS, both right and left in women. No relationship was observed between crPWV, FMD, CIMT, and SUA.

Early Post-Transplant Leptin Concentration Changes in Kidney Transplant Recipients.

Background and Objectives: Kidney transplant recipients represent a unique population with metabolic abnormalities, altered nutritional and immune status, as well as an imbalanced regulation of adipocytokine metabolism. Leptin is a hormonally active protein mainly produced by fat tissue that modulates appetite, satiety, and influences growth, energy, and bone metabolism. There has been great interest in the role of this hormone in chronic kidney disease-related protein energy wasting; thus, a positive leptin correlation with body mass index and fat mass was confirmed. This study was designed to determine the association of pre and post-kidney transplant leptin concentration with nutritional status and body composition. Materials and Methods: We studied 65 kidney transplant recipients. Nutritional status was evaluated before kidney transplantation and 6 months later using three different malnutrition screening tools (Subjective Global Assessment Scale (SGA), Malnutrition Inflammation Score (MIS), and Geriatric Nutritional Risk Index (GNRI)), anthropometric measurements, and body composition (bioelectrical impedance analysis (BIA)). Demographic profile, serum leptin levels, and other biochemical nutritional markers were collected. Statistical analysis was performed with R software. Results: Median age of the studied patients was 45 years, 42% were females, and 12% had diabetes. Leptin change was associated with body weight (p < 0.001), waist circumference (p < 0.001), fat mass (p < 0.001) and body fat percentage (p < 0.001), decrease in parathyroid hormone (PTH) (p < 0.001) transferrin (p < 0.001), diabetes mellitus (p = 0.010), and residual renal function (p = 0.039), but not dependent on dialysis vintage, estimated glomerular filtration rate (eGFR), or delayed graft function at any time during the study. After adjustment for age and sex, body mass index (BMI) (p < 0.001), fat mass (p < 0.001), and body fat percentage (p < 0.001) were independent variables significantly associated with post-transplant leptin change. Lower leptin values were found both before and after kidney transplantation in the SGA B group. GNRI as a nutritional status tool was strongly positively related to changes in leptin within the 6-month follow-up period. Conclusions: Kidney transplant recipients experience change in leptin concentration mainly due to an increase in fat mass and loss of muscle mass. GNRI score as compared to SGA or MIS score identifies patients in whom leptin concentration is increasing alongside an accumulation of fat and decreasing muscle mass. Leptin concentration evaluation in combination with BIA, handgrip strength measurement, and GNRI assessment are tools of importance in defining nutrition status in the early post-kidney transplant period.

Should we calculate arterial stiffness gradient in middle-aged women with increased cardiovascular risk?

PURPOSE: The study was designed to evaluate clinical and laboratory determinants pulse wave velocity (PWV) ratio in women at the age of 50-65 years without overt cardiovascular disease but having elevated cardiovascular risk, such as hypertension, obesity, diabetes and hypercholesterolemia. MATERIALS AND METHODS: We analyzed data from 1170 women enrolled in the national-wide primary prevention program. Univariate and multivariate linear regression analysis was used to establish independent risk factors in groups based on clinical data, laboratory values, and comorbidities. Arterial stiffness was evaluated using applanation tonometry technique (SphygmoCor). The PWV ratio was calculated by dividing cfPWV to crPWV. RESULTS: In multivariate logistic regression analysis, age (OR = 1.109, p < .001), waist circumference (OR = 1.021, p = .001) and mean arterial pressure (OR = 1.031, p < .001) were found as independent clinical determinants of PWV ratio, while independent laboratory determinants were urine albumin to creatinine ratio (OR = 1.189, p = .010), triglycerides (OR = 1.161, p = .034), glucose (OR = 1.28, p = .001) and eGFR (OR = 0.998, p = .007). Diabetes (OR = 1.811, p = .029), hypertension (OR = 2.784, p = .042) and menopause (OR = 1.054, p = .018) were established as independent factors in comorbidities group. The analysis confirmed that PWV ratio (R2 = 0.0667, p < .001), as well as carotid radial (R2 = 0.0341, p < .001) and carotid femoral PWV (R2 = 0.1752, p < .001) is affected by mean arterial blood pressure. CONCLUSIONS: Age, abdominal obesity, blood pressure, triglycerides, glucose, kidney function parameters and menopause all are associated with PWV ratio. More importance to women with high cardiovascular risk should be given whilst screening and stratifying further progression of the disease.

Two years of maintenance hemodialysis has a pronounced effect on arterial stiffness progression.

BACKGROUND: The change of aortic stiffness, but not the particular baseline value, plays a crucial role in estimating the patient risk with end-stage renal disease. Therefore, we aimed to analyze the evolution of central and peripheral arterial stiffness in hemodialysis population without previous cardiovascular events during a 2-year follow-up. METHODS: 60 hemodialysis patients (mean age 57.61 ± 13.01 years) were prospectively interviewed, and they underwent blood tests, chest X-ray for aortic calcification evaluation and pulse wave velocity (PWV) measurements at the baseline, after 6 months and after 2 years of observation period. RESULTS: We found significant progression of aortic PWV (12.73 vs. 14.24 m/s, p = 0.032) and regression of brachial PWV (11.53 vs. 8.85 m/s, p < 0.001). CRP increase influenced evolution of aortic PWV (ß = 0.331, p = 0.031, R2 = 0.599). Higher ß2-microglobulin values was related to the progression of aortic PWV (ß = 0.219, p = 0.022, R2 = 0.568). Mean arterial blood pressure had influence only on the short-term arterial stiffness evolution. CONCLUSIONS: Patients on maintenance hemodialysis experience pronounced changes of arterial stiffness during the 2-year follow-up period. The progression of aortic stiffness is related to inflammatory response and particularly is influenced by ß2-microglobulin concentration and aortic calcification.

Mismatch between stiffness in elastic and muscular arteries as a predictor of vascular calcification in dialysis patients.

BACKGROUND: Vascular calcification is one of the risk factors for arterial stiffness in patients with chronic kidney disease. We hypothesized that a mismatch between elastic and muscular arteries, represented as pulse wave velocity (PWV) ratio, could depict the extent of vascular calcification in end-stage renal disease. We also aimed to compare the predictive PWV ratio value to other factors possibly related to vascular calcification in dialysis population. METHODS: In this cross-sectional study, in 60 chronic dialysis patients without previous cerebrovascular events, cardiovascular disease and events or clinically evident peripheral artery disease (ankle-brachial index >0.9), carotid-femoral and carotid-radial PWV as well as central hemodynamic parameters were measured by applanation tonometry (SphygmoCor). The PWV ratio using carotid-femoral PWV divided by carotid-radial PWV was calculated. Each patient underwent blood tests and chest X-ray for aortic arch calcification scoring. Two experienced radiologists blinded to patient's medical data evaluated chest X-rays (Cohen's kappa coefficient 0.76) and calculated how many sectors were calcified (Ogawa et al. in Hemodial Int 13:301-306, 2009). Differently scored chest X-rays were repeatedly reviewed and a consensus was reached. RESULTS: The study population consisted of 31 (51.7%) males and 29 (48.3%) females, mean age 52.73 ± 13.76 years. Increased risk for aortic arch calcification was associated with higher PWV ratio even after adjustment for age, height, heart rate, ferritin level and C-reactive protein level (OR 2.59E+04, 95% CI 2.43E+01, 2.65E+09, p = 0.021). PWV ratio together with above-mentioned variables could predict the presence of aortic arch calcification with specificity of 93% (95% CI 78, 99%) and sensitivity of 53% (95% CI 34, 72%). CONCLUSION: The elastic and muscular arteries' stiffness mismatch was strongly associated with the extent of aortic arch calcification in this dialysis population and had better calcification predictive value compared to other demographic, hemodynamic and biochemical markers.

Usefulness of pretransplant aortic arch calcification evaluation for kidney transplant outcome prediction in one year follow-up.

Vascular calcification (VC) is linked to post-transplant cardiovascular events and hypercalcemia which may influence kidney graft function in the long term. We aimed to evaluate whether pretransplant aortic arch calcification (AoAC) can predict post-transplant cardiovascular or cerebrovascular events (CVEs), and to assess its association with post-transplant plasma calcium levels and renal function in one-year follow-up. Our single-center observational prospective study enrolled 37 kidney transplant recipients (KTR) without previous history of vascular events. Two radiologists evaluated pretransplant AoAC on chest X-ray as suggested by Ogawa et al. in 2009. Cohen's kappa coefficient was 0.71. The mismatching results were repeatedly reviewed and resulted in consensus. Carotid-femoral (cfPWV) and carotid-radial pulse wave velocity (crPWV) was measured using applanation tonometry before and one year after transplantation. Patient clinical, biochemical data, and cardiovascular/CVE rate were monitored within 1 year. We found out that eGFR1year correlated with eGFRdischarge and calcium based on hospital discharge data (ß = 0.563, p = .004 and ß = 51.360, p = .026, respectively). Multivariate linear regression revealed that donor age, donor gender, and recipient eGFRdischarge (R-squared 0.65, p = .002) better predict eGFR1year than AoAC combined with recipient eGFRdischarge (R-squared 0.35, p = .006). During 1-year follow-up, four (10.81%) patients experienced cardiovascular events, which were predicted by PWV ratio (HR 7.549, p = .045), but not related to AoAC score (HR 1.044, p = .158). In conclusion, KTR without previous vascular events have quite low cardiovascular/CVE rate within 1-year follow-up. VC evaluated as AoAC on pretransplant chest X-ray together with recipient eGFRdischarge could be related to kidney function in one-year follow-up.

Histopathological Classification-A Prognostic Tool for Rapidly Progressive Glomerulonephritis.

Background: Recently proposed histopathological classification may predict patient outcome in pauci-immune glomerulonephritis. This study sought to prove that the prognostic effect could be extended to all types of rapidly progressive glomerulonephritis. Methods: Retrospective analysis of patients diagnosed with rapidly progressive glomerulonephritis between April 1999 and August 2015 was performed. Epidemiological and clinical data were collected from medical records. The descriptions of renal biopsies were reviewed and classified into focal, sclerotic, crescentic and mixed class according to classification proposed by Berden et al. The study end points were end stage renal disease (ESRD) or death. Survival analyses were modelled using Cox regression. Results: 73 renal biopsies with diagnosis of rapidly progressive glomerulonephritis were included in the study. 25 (34.2%), 16 (21.9%), 24 (32.9%) and 8 (11%) patients were assigned to focal, crescentic, mixed and sclerotic class, respectively. Thirty-two (42.5%) patients were anti-neutrophil cytoplasmic antibody (ANCA) negative, of which eight (10.9%) were anti⁻glomerular basement membrane antibody (anti⁻GBM) positive and 24 (32.8%) were negative for autoimmune antibodies. Six (8.2%) patients died within one year. Among patients who survived, median change in estimated glomerular filtration rate (eGFR) values were: -10.5 mL/min in focal, 4.2 mL/min in crescentic, -4.3 mL/min in mixed and 4.1 mL/min in sclerotic group, p > 0.05. In the Cox regression model, there was no significant predictor of patient survival whereas the sclerotic group (HR 3.679, 95% CI, 1.164⁻11.628, p < 0.05) and baseline eGFR of <15 mL/min (HR 4.832, 95% CI, 1.55⁻15.08, p < 0.01) had an unfavorable effect for renal survival. Conclusions: Predominant glomerular sclerosis and low eGFR at baseline are associated with higher risk of ESRD in cases with crescentic glomerulonephritis. Therefore, despite the origin of injury, histological classification might aid in prediction of patient outcomes in rapidly progressive glomerulonephritis.

Associations between birth weight and adult apolipoproteins: The LifeGene cohort.

BACKGROUND: Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort. METHODS: The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801). RESULTS: The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005). CONCLUSIONS: Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.

Aortic Stiffness Can be Predicted From Different eGFR Formulas With Long Follow-Up in the Malmö Diet Cancer Study.

We studied the impact of estimated glomerular filtration rate (eGFR) based on either creatinine or cystatin C, or in combination, on vascular aging (aortic stiffness) and central hemodynamics (central systolic blood pressure) in a Swedish urban population with median 17 years of follow-up. Participants (n = 5049) from the population-based Malmö Diet and Cancer Study that underwent baseline examination and later participated in the prospective cardiovascular arm were selected. Of these, 2064 with measured carotid-femoral pulse wave velocity (cfPWV) and central blood pressure at follow-up were enrolled. eGFR was calculated using cystatin C (eGFRCYS) and creatinine (eGFRCR) equations: Caucasian, Asian, pediatric, and adult cohorts (CAPA), the Lund-Malmö revised (LMrev), and the European Kidney Function Consortium (EKFC) equations. Lower adjusted eGFRCR, but not eGFRCYS, were independently associated with higher cfPWV (P < .001, respectively). eGFR <60 mL/min/1.73 m2 determined higher cfPWV except when using the EKFC equation. Conversely, CAPA/LMrev and CAPA/EKFC ratios were not associated with aortic stiffness. Lower eGFRCR is associated with higher future aortic stiffness independently of age, sex, heart rate, mean blood pressure, body mass index, and antihypertensive treatment. The ratio of eGFRCYS and eGFRCR equations could not predict aortic stiffness at all.