Leonor Rivera

Homocysteine levels in morbidly obese patients. Its association with waist circumference and insulin resistance

The association between morbid obesity and hyperhomocysteinemia (HH) remains controversial and the nature of this relationship needs to be clarified as several metabolic, lipidic, inflammatory and anthropometric alterations that accompany morbid obesity may be involved. In 66 morbidly obese patients, 47 women and 19 men aged 41 ± 12 years and 66 normo-weight subjects, 43 women and 23 men, aged 45 ± 11 years, we determined homocysteine (Hcy) levels along with lipidic, anthropometric, inflammatory and insulin resistance markers. In addition, we investigated the effect of Metabolic Syndrome (MS) and its components on Hcy levels. Obese patients had statistically higher Hcy levels than controls: 12.76 ± 5.30 μM vs. 10.67 ± 2.50 μM; p = 0.006. Moreover, morbidly obese subjects showed higher waist circumference, glucose, insulin, HOMA, leptin, triglycerides, fibrinogen, C reactive protein (CRP) (p < 0.001, respectively), and lower vitamin B12 (p = 0.002), folic acid and HDL-cholesterol (p < 0.001, respectively). In the multivariate regression analysis, waist circumference, glucose, leptin and folic acid levels were independent predictors for Hcy values (p < 0.050). When obese patients were classified as having MS or not, no differences in Hcy levels were found between the two groups (p = 0.752). Yet when we analysed separately each MS component, only abdominal obesity was associated with Hcy levels (p = 0.031). Moreover when considering glucose >110 mg/dL (NCEP-ATPIII criteria) instead of glucose intolerance >100 mg/dl (updated ATPIII criteria), it also was associated with HH (p = 0.042). These results were confirmed in the logistic regression analysis where abdominal obesity and glucose >115 mg/dL constitute independent predictors for HH (OR = 3.2; CI: 1.23-13.2; p = 0.032, OR: 4.6; CI: 1.7-22.2; p = 0.016, respectively). The results of our study indicate that increased Hcy levels are related mostly with abdominal obesity and with insulin resistance. Thus, HH may raise atherothrombotic and thromboembolic risk in these patients.

Red Blood Cell Distribution Width in Patients With Cryptogenic Stroke

Background: There is no information about a possible association of red blood cell distribution width (RDW) with cryptogenic stroke (CS). We aimed to analyze the association of RDW with CS. Patients and Methods: One hundred and sixty-three patients with CS were included along with 186 healthy controls. Fibrinogen, leukocytes, hemoglobin, and erythrocyte indices were evaluated. Results: Patients showed higher RDW, leukocyte count, and body mass index (BMI) than controls (P < .05). No differences were observed in the erythrocyte indices or in glucose, cholesterol, and triglycerides levels (P > .05). When patients with anemia were excluded from the study (6 controls and 5 cases), the differences between cases and controls persisted (P = .005). Multivariate logistic regression revealed that, after adjusting for potential confounders (anemia, age > 40 years, gender, and fibrinogen >382 mg/dL, total cholesterol >240 mg/dL, and BMI > 28.7 kg/m2), RDW >14% was the only parameter that independently increased the risk of CS. Conclusion: The RDW >14% increased the risk of CS by 2.5-fold, irrespectively of anemia, inflammation, and lipidic profile.

Haematological, biochemical and inflammatory parameters in inactive Behçet's disease. Its association with red blood cell distribution width

Red blood cell distribution width (RDW) has been shown to be associated with disease activity in several inflammatory disorders. However only one study to show this has been conducted in patients with Behçets disease (BD). The aim of the present study was to analyse the association of RDW with BD and its main complications; i.e.; thrombosis and posterior uveitis. A second aim was to analyse the possible correlation between RDW and both haematological and inflammatory parameters. Eighty-nine patients with BD (48 males/41 females) and 94 controls (49 males/45 females) were included in the study. Patients were in an inactive phase of the disease, showing only minimum activity. RDW was statistically higher in patients than in controls (14.02 ± 1.32 vs. 13.15 ± 0.75; p < 0.001) as were CRP, fibrinogen, leucocytes and neutrophils (p < 0.001). No differences in haematimetric indices (MCV, MCH, MCHC) were observed (p > 0.05). RDW correlated negatively with haemoglobin, MCH and MCHC (p < 0.05), and directly with homocysteine (p < 0.01). No correlation was found between RDW and the several inflammatory parameters analysed (p > 0.05). The multivariate regression analysis revealed that haemoglobin and homocysteine were independent predictors of RDW (beta coefficient: -0.310; p = 0.003, beta coefficient: 0.379; p < 0.001, respectively). RDW >14 was associated with neither thrombosis nor uveitis (p = 0.935; p = 0.553, respectively). Our results indicate that BD patients show increased RDW when compared with controls. This increase seems to be related with haematimetric indices and with homocysteine levels. Lack of correlation with inflammatory markers may be due to the fact that patients were in an inactive phase of the disease.

Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients

OBJECTIVE Red blood cell distribution width (RDW) is a hematological parameter that has been studied in several clinical settings and has been found to be related to both anemia and inflammatory status. As obesity is related to increased inflammatory pattern, we aimed to analyze the RDW in this setting. METHODS We determined hematological and inflammatory parameters in morbidly obese patients before bariatric surgery (n=142) and normo-weight controls (n=144). RESULTS RDW was higher in patients than in controls (p<0.001), along with C-reactive protein (p<0.001) and fibrinogen, (p<0.001) while hemoglobin (p=0.026), serum iron (p<0.001), MCH (p=0.002) and MCHC (p<0.001) were lower in morbidly obese patients. The logistic correlation analysis revealed that only low serum iron (<62 μg/dL) and MCH (<28.14 pg) levels were associated with RDW>14% (OR 7.61, 95% CI: 1.93-30.04, p=0.004; OR 5.67, 95% CI: 1.98-16.24, p=0.001; respectively). CONCLUSIONS These data indicate that the elevated RDW in morbidly obese patients reflects a mild red blood cell hypochromia that does not relate to inflammatory parameters, but to hyposideremia and, consequently, to lower erythrocyte indices, possibly as a result of being on a very low-calorie diet before bariatric surgery. Therefore, RDW should not be considered as an inflammatory marker in this clinical setting.

Association of erythrocyte deformability with red blood cell distribution width in metabolic diseases and thalassemia trait

Increased red blood distribution width (RDW) in anemia is related to disturbances in the cellular surface/volume ratio, usually accompanied by morphological alterations, while it has been shown in inflammatory diseases that the activity of pro-inflammatory cytokines disturbing erythropoiesis increases RDW. Recently it has been reported that higher RDW is related with decreased erythrocyte deformability, and that it could be related with the association of RDW and increased risk of cardiovascular diseases. In order to analyze the influence of morphological alterations and proinflammatory status on the relationship between RDW and erythrocyte deformability, we analyzed erythrocyte deformability along with RDW and other hematological and biochemical parameters in 36 α-thalassemia, 20 β-thalassemia, 20 δβ-thalassemia trait carriers, 61 metabolic syndrome patients and 76 morbidly obese patients. RDW correlated inversely with erythrocyte deformability in minor β-thalassemia (r =-0.530, p <  0.05), and directly in both metabolic syndrome and morbidly obese patients (ρ= 0.270, p <  0.05 and ρ= 0.258, p <  0.05, respectively). Minor β-thalassemia is often accompanied by more marked cell-shaped perturbations than other thalassemia traits. This could be the reason for this negative association only in this setting. Higher anisocytosis seems to be associated with greater morphologic alterations (shape/volume), which reduce erythrocyte deformability. The proinflammatory profile in metabolic patients can be related to the positive association of RDW with erythrocyte deformability found in these patients. However, further research is needed to explain the mechanisms underlying this association.

Association of metabolic syndrome and its components with hyperuricemia in a Mediterranean population.

Several studies have found an association between hyperuricemia and metabolic syndrome (MS), although there are discrepancies as to which MS components play a pivotal role in this association. We aimed to investigate the association between serum uric acid (SUA) levels and MS in a Mediterranean population (eastern Spain). We performed a case-control study of 71 patients with MS and 122 healthy controls. MS was defined according to the revised National Cholesterol Education Program Adult Treatment Panel III modified criteria. Hyperuricemia was defined as SUA levels >6.55 mg/dL. We determined biochemical, lipidic and inflammatory parameters along with uric acid. Patients with MS showed a higher risk of hyperuricemia than those without MS (OR: 2.87 95% CI: 1.48- 5.55; p = 0.002). In turn, the unadjusted logistic regression analysis showed that hyperuricemia is associated with a higher risk of presenting all the MS components, except hypertension; i.e., hypertriglyceridemia, low HDL-cholesterol, abdominal obesity and glucose intolerance were predictors for hyperuricemia (OR: 3.15, 95% CI: 1.61- 6.15, p = 0.001; OR: 4.07, 95% CI: 1.77- 9.33, p = 0.001; OR: 2.81, 95% CI: 1.41- 5.58, p = 0.003 and OR: 2.82, 95% CI: 1.46- 5.45, p = 0.002 respectively). The adjusted logistic regression analysis revealed that only low HDL-cholesterol and glucose intolerance were independent predictors for hyperuricemia (OR: 2.71, 95% CI 1.06- 6.97, p = 0.038; OR: 2.14, 95% CI 1.01- 4.56, p = 0.049, respectively). In our geographical area, the patients with MS showed a nearly 3-fold risk of hyperuricemia than those without. Among all the MS components, low-HDL-cholesterol and high glucose independently increased more than twice the risk of hyperuricemia, and are the pivotal components involved in hyperuricemia.

Influence of age and gender on red blood cell distribution width.

Keywords: agin gender g; ed ; r blood cell distribution width. Tothe Editor, We have read with interest the recently published article by Lippi et al. [1] in Clinical Chemistry and Laboratory Medicine about red blood cell distribution width (RDW) and its association with age and gender. RDW is an inex-pensive, easy to calculate parameter that reflects aniso-cytosis which, in recent years, has received growing attention [2] . High RDW has been found to be associated with multiple conditions, such as cardiovascular events [3, 4] or inflammatory diseases [5, 6] . In the paper by Lippi et al. [1] , a strong dependence of RDW upon age and gender is shown in a large popula-tion (n = 1907) of actual and former healthy blood donors. The authors presented evidence of an important associa-tion of increasing RDW with aging. More interestingly, they reported that the proportion of subjects with RDW higher than 14.6% (considered as a biomarker of morbid-ity and mortality in general population [7] ) increased from 6% in < 41 years up to 75% in those older than 90 years [1] . These findings could carry important implications in clinical practice and research dealing with RDW and its association with several conditions, as age (and gender) should be considered an important confounding factor. However, the data reported by Lippi et al. [1] should be carefully evaluated since their sample, although free of diseases, is composed of blood donors in whom habitual marrow stimulation could have an effect on RDW values. This could lead to overestimating the effect of aging on RDW. To further clarify this issue, we have retrospectively analyzed data retrieved from 809 healthy subjects (380 males/429 females) belonging to the La Fe University Hospital staff at the Preventive Medicine Service between 2008 and 2013 to investigate the association of RDW with age and gender. The subjects were explored for diseases and a routine biochemical panel was performed to further discard subjacent conditions. Exclusion criteria included organic (hepatic, cardiac, liver or renal disease), malig-nant, hematological, infectious or inflammatory disease, previous history of ischemic heart disease or stroke, previ-ous thromboembolism, treatment with rheological drugs and secondary obesity (hypothyroidism, Cushing syn-drome) and anemia. Mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), hemoglobin and RDW were deter-mined with the hematological autoanalyzer Sysmex XE-2100 (Kobe, Japan). The normality of distributions was analyzed using the Kolgomorov-Smirnov test. The Kruskal-Wallis test with Dunn ’ s comparisons was used to compare the median values of RDW between age groups ( < 20, 20 – 29, 30 – 39, 40 – 4, 950 – 5, 960 – 6, 9 ≥ 0). 7The Mann-Whitney test was used to compare median values between genders in each age group. In addition, the proportion of subjects with RDW higher than 14.6% among age groups was compared using the χ 2 est -t . The association between variables was explored by means of Spearman ’ s correlation coefficient ( ρ ) and multivariate regression analysis, being RDW the dependent variable and hemoglobin, MCV, MCH, gender and age independ-ent variables [adjusted β coefficients ( β *) have been reported]. Statistical analyses were performed using the SPSS (IBM Corporation, Armonk, NY, USA) and Graphpad

Reply to "The association of red blood cell distribution width and morbid obesity" by Aydin et al.

We thank Aydin & cols. for their comments about our recently published paper “Red blood cell distribution width is not related with inflammatory parameters in morbidly obese patients” in Clinical Biochemistry Journal [1]. The authors show their concern about the clinical interpretation of our findings since we did not report folate and B12 vitamin levels. Moreover, they state that we should demonstrate the elimination of thrombocytopenic diseases by showing platelet count data. Aswe state in the paper, exclusion criteria for obese patients included “organic, malignant, hematological, infectious or inflammatory disease”. Therefore, any case of thrombocytopenic disease was not included. Moreover, obese patients showed higher levels of platelets (control: 225±45×10/μL, obese: 258±55×10/μL, p b 0.001) althoughwithin normal range and congruent with amild inflammatory status. Obese patients showed a discrete lowered folate (control: 9.26 ± 4.61 ng/mL, obese: 5.71 ± 2.59 ng/mL, p b 0.001) and B12 vitamin (control: 534 ± 192 pg/mL, obese: 429 ± 177 pg/mL, p = 0.001), which might indicate nutritional deficiencies. But when these variables were included in the multivariate logistic regression analysis, no effect on the reported model was observed. This data further reinforce our conclusion that hyposideremia, rather than inflammatory parameters, is related with higher RDW in these patients. However, the role of nutritional deficiencies in this clinical setting should be taking into account when hematological parameters are explored.