High intraindividual variation of B-type natriuretic peptide (BNP) and amino-terminal proBNP in patients with stable chronic heart failure.

BACKGROUND: Plasma B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) are promising markers for heart failure diagnosis, prognosis, and treatment. Insufficient data on the intraindividual biological variation (CV(i)) of BNP and NT-proBNP hamper interpretation of changes in concentration on disease progression or treatment optimization. We therefore investigated CV(i) values in stable heart failure patients. METHODS: We recruited 43 patients with stable chronic heart failure living in Curacao (22 males, 21 females; median age, 63 years; range, 20-86 years; New York Heart Association classes I-III). Samples were collected for within-day CV(i) (n = 6; every 2 h starting at 0800), day-to-day CV(i) (n = 5; samples collected between 0800 and 1000 on 5 consecutive days), and week-to-week CV(i) (n = 6; samples collected between 0800 and 1000 on the same day of the week for 6 consecutive weeks). NT-proBNP (Roche) and BNP (Abbott) were measured by immunoassay. RESULTS: Median (range) concentrations were 134 (0-1630) ng/L (BNP) and 570 (17-5048) ng/L (NT-proBNP). Analytical variation, week-to-week CV(i), and reference change values were 8.4%, 40%, and 113% (BNP), and 3.0%, 35%, and 98% (NT-proBNP). Week-to week CV(i)s were inversely related to median BNP concentrations. Week-to week CV(i)s for BNP were 44% (BNP < or =350 ng/L) and 30% (BNP >350 ng/L). Both BNP and NT-proBNP increased between 0800 and 1000. Median NT-proBNP/BNP ratios were inversely related to median BNP concentrations. CONCLUSIONS: The high CV(i)s hamper interpretation of changes in BNP and NT-proBNP concentrations and may partly explain their poor diagnostic values in chronic heart failure. Easily modifiable determinants to lower CV(i) have not been identified. The value of BNP and NT-proBNP for chronic heart failure diagnosis, and especially for follow-up and treatment optimization of individuals, remains largely to be established.

Evidence for a metabolic shift of arginine metabolism in sickle cell disease.

Over the last few years, a pivotal role has been ascribed to reduced nitric oxide (NO) availability as a contributing factor to the vaso-occlusive process of sickle cell disease. We investigated whether arginine metabolism in sickle cell patients is different from healthy controls. Blood samples were drawn by venipuncture in the fasting state from 8 clinically asymptomatic HbSS patients and 14 race-matched HbAA controls. HbSS patients had decreased plasma arginine (p=0.001) and increased proline (p=0.015) levels as compared to controls. Ratios of arginine to ornithine (p<0.001), proline (p<0.001), glutamate (p=0.003), and citrulline (p=0.026) were lower in HbSS patients. There were significant correlations of ornithine (r(s)=-0.71, p=0.047), citrulline (r(s)=-0.79, p=0.021), arginine/ornithine (r(s)=0.93, p=0.001), and arginine/citrulline (r(s)=0.81, p=0.015) to hemoglobin and of arginine/proline (r(s)=-0.76, p=0.028) and citrulline (r(s)=0.71, p=0.048) to leukocyte counts. These data indicate that in clinically asymptomatic sickle cell patients increased arginine metabolism is shifted to the arginase pathway and that this seems to be more profound in patients with higher hemolytic rates and leukocyte counts.

The association of pre-eclampsia with the Duffy negative phenotype in women of West African descent.

OBJECTIVE: To investigate whether pre-eclampsia in Curaçao is associated with the Duffy negative phenotype. DESIGN: Retrospective study. RESULTS: Women with a history of pre-eclampsia had a higher Duffy negative phenotype frequency compared with women with a history of uncomplicated pregnancies (52.8 vs 27.3%, respectively; odds ratio 2.98; 95% CI 1.40-6.32; P = 0.004). CONCLUSIONS: Pre-eclampsia is associated with the Duffy negative phenotype in women of West-African descent in the island of Curaçao.

Optimization of folic acid, vitamin B(12), and vitamin B(6) supplements in pediatric patients with sickle cell disease.

Using homocysteine as a functional marker, we determined optimal folic acid, vitamin B(12), and vitamin B(6) dosages in 21 pediatric sickle cell disease (SCD) patients (11 HbSS, 10 HbSC; 7-16 years). Daily supplements of folic acid (400, 700, or 1,000 microg), vitamin B(12) (1, 3, or 5 U.S. 1989 RDA), and vitamin B(6) (1 or 3 U.S. 1989 RDA) were gradually increased in an 82-week dose-escalation study. Blood was taken at 9 occasions for measurements of erythrocyte (RBC) and serum folate, plasma vitamin B(12), whole-blood vitamin B(6), and plasma homocysteine. Augmentation of folic acid from 700 to 1,000 microg and vitamin B(12) from 3 to 5 RDA did not further decrease homocysteine. Percentages of patients exhibiting significant individual homocysteine decreases amounted to 43% (folic acid from 0 to 400 microg, vitamins B(12) and B(6) from 0 to 1 RDA), 14% (folic acid from 400 to 700 microg), 24% (vitamin B(12) from 1 to 3 RDA), and 18% (vitamin B(6) from 1 to 3 RDA ). The lowest plasma homocysteine at 82 weeks was 5.9 +/- 2.2 micromol/L. Patients with HbSS had higher RBC folate than HbSC. The entire group exhibited an inverse relation between RBC folate and hemoglobin. We conclude that RBC folate is less valuable for folate status assessment in SCD patients. Optimal dosages are as follows: 700 microg folic acid (3.5-7 U.S. 1989 RDA), 3 U.S. 1989 RDA vitamin B(12) (4.2-6.0 microg), and 3 U.S. 1989 RDA vitamin B(6) (4.2-6.0 mg). A practical daily combination is 1 mg folic acid (4.3-8.5 U.S. 1998 RDA when taken with meals), 6 microg vitamin B(12) (2.5-5 U.S. 1998 RDA), and 6 mg vitamin B(6) (4.6-10 U.S. 1998 RDA). This combination may by simple and relatively inexpensive means reduce these patients' inherently high risk of endothelial damage.

High serum interleukin-8 levels in afro-caribbean women with pre-eclampsia. Relations with tumor necrosis factor-alpha, duffy negative phenotype and von Willebrand factor.

PROBLEM: Pre-eclampsia is characterized by neutrophil activation. Interleukin-8 (IL-8) is a strong neutrophil chemo-attractant and activator. METHOD OF STUDY: We measured serum IL-8 in 13 pre-eclamptic Afro-Caribbean women and 13 gestational age-, race- and parity-matched normotensive and non-proteinuric controls. We also determined serum tumor necrosis factor-alpha (TNF-alpha), the phenotypes of the IL-8 binding Duffy blood group antigen receptor and the von Willebrand factor (vWF) plasma levels. RESULTS: Serum IL-8, TNF-alpha, Duffy negative phenotype frequency and plasma vWF were higher in pre-eclamptic women compared with controls. IL-8 correlated positively with both TNF-alpha and vWF in the entire study group. CONCLUSIONS: Higher IL-8 levels in pre-eclampsia may result from increased production (secondary to increased TNF-alpha levels) and/or reduced clearance (related to a high frequency of Duffy negative phenotype).

Enhanced sVCAM-1 levels in paediatric patients with sickle cell disease

Recently, several reports have shown endothelial activation to play an important role in the pathophysiology of sickle cell vaso-occlusion. We measured serum soluble VCAM-1 and soluble ICAM-I levels in steady state paediatric sickle cell patients. TNF, an endothelial activating cytokine, was also measured. sVCAM-I levels were increased as compared to age, sex and race-matched controls (p=0.002), whereas sICAM-I levels were not significantly enhanced. TNF levels were also elevated in paediatric sickle cell patients as compared to controls (p=0.01). These results show that endothelial activation is already manifest at a very young age in sickle cell patients, probably resulting from enhanced endothelial activating cytokines, such as TNF.(AU)

Folic acid status of paediatric patients with sickle cell disease

We investigated whether paediatric patients with sickle cell disease (9ñ4 years; 27 HbSS; 19 HbSC) have different folic acid status compared with age-, sex-and race-matched HbAA controls (n=20), and whether their folic acid status can be improved by folic acid supplementation. The patients were supplemented with vitamins B6 and B12 during one week and with folic acid during the next week. Circulating folic acid, homocysteine, vitamin B6 and vitamin B12 levels were measured at baseline (patients and controls), after 1 and 2 weeks (patients). The patients had similar folic acid, vitamin B6 and vitamin B12, but higher homocysteine levels, compared with HbAA controls (12.7ñ4.5 vs 10.9ñ3.5 mmol/l;p=0.04). Vitamin B6 and B12 supplementation did not change their homocysteine levels, but folic acid supplementation caused a 52 percent reduction (to 5.7ñ1.6). We conclude that patients with sickle cell disease have adequate vitamin B6 and B12 status, but suboptimal folic acid status. They may benefit from folic acid supplementation to reduce their high risk for endothelial damage.(AU)

Umbilical vessels in preeclamptic pregnancies have low contents of both w3 and w6 long chain polyunsaturated fatty acids

We determined the fatty acid compositions of maternal and umbilical platelets (PLT), and of the umbilical arteries (UA) and veins (UV) of 27 preeclamptic pregnancies and 24 normotensive controls, mostly of Afro-Caribbean descents. Between-group differences were analyzed with the Kruskal-Wallis test or with analysis of convariance with gestational age as covariate. PLT of preeclamptic women contained lower 20:5 w3, and a higher 20.4 w6/20:5 w3 ratio. Linear discriminant analysis revealed higher 20:4 w6. Major differences were found in UV and especially UA fatty acid compositions. UA and UV of preeclamptic pregnancies contained lower long chain polyunsaturated fatty acids of the w3-series (LCPUFA w3), LCPUFA w6 and 20:3 w6. UA had lower 20:4 w6 higher 20:3 w9 and 20:3 w9/20:4 w6. We conclude that the low LCPUFA w3 and LCPUFA w6 levels in umbilical vessels of preeclamptic women with adequate w6 status may indicate insufficient LCPUFA transplacental transfer. The low 20:4 w6, high 20:3 w9 and high 20:3 w9/20:4 w6 ratio in UA may unfavourably affect local prostacylin production and cause other 20:3 w9 related adverse effects. Low 20:3 w6 in UV and UA, and low 20:5 w3 in maternal PLT, may contribute to the dominance of 20:4 w6 derived eicosanoids.(AU)

The dietary fatty acids of patients with coronary artery disease and control in Curacao: implications for primary and secondary prevention

Patients with coronary artery diseases are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 ñ 10 years) in Curacao is higher as compared with 77 controls (51 males, 26 females; ages 56 ñ 7 years). For this, we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty acid composition of the preceeding weeks. Patients with coronary artery disease and controls had minor differences in cholesterol ester fatty acids. Their cholesterol ester linoleic acid content suggests that the dietary polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data reported for the the Netherlands, Greenland and Crete showed that the dietary fatty acid composition in Curacao is typically Western with a high intake of saturated fatty acids, a low intake of monounsaturated fatty acids and the consumption of linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain polyunsaturated fatty acids from fatty fish is low. Reduction of dietary saturated fatty acids, augmentation of fish consumption, and an increase of the O-linolenic/linoleic acid ratio are likely to be of benefit to both primary and secondary prevention from coronary artery disease in Curaco.(AU)

Serum calcium and vitamin D status of patients with sickle cell disease in Curacao: comparison with Saudi Arabia

Data from Saudi Arabia suggest that low vitamin D status is involved in skeletal abnormalities of patients with homozygous sickle-cell disease (HbSS). We measured parameters of calcium homeostasis and vitamin D status in HbSS patients (median age: 8 years, range: 3-19; 8 females, 10 males) and matched HbAA controls living in the tropical island of Curacao. Serum calcium of HbSS patients (2.32 ñ 0.07 mmol/l) was lower (ANCOVA, p = 0.002) than that of HbAA controls (2.44 ñ 0.14). None of the subjects had hypocalcaemia. There were no differences in phosphate, total protein, albumin, intact parathyroid hormone (PTH), 25-hydroxyvitamin D [25(OH)D; HbSS 87 ñ 27, HbAA 86 ñ 15 nmol/l] and 1,25-dihydroxyvitamin D. There were no significant relationships between serum calcium and albumin, calcium and total protein, and PTH and 25 (OH)D. Our data suggest that hypocalcaemia and hyperparathyroidic tendencies in Saudi Arabian HbSS patients are likely to be caused by the locally poor vitamin D status, attributable to insufficient exposure to direct sunlight (AU)

Low sickle-cell linoleic acid content is related to young erythrocyte age - abstract

Erythrocyte (RBC) fatty acids (FA) and polyamines were determined in subjects with HvM (n=29), HbAC (3), HbAS (41), HbSC (25) and HbSS (19). FA of plasma cholesterol esters (CE), plasma phosphatidylcholines (PC), RBC PC, and plasma and RBC PC-species were studied in subgroups. RBC of patients with HbSS and HbSC had abnormal FA, PC-FA, PC-species and polyamines. There were no major differences in plasma CE-FA, PC-FA and PC-species. Low 18:2U6 in RBC, RBC PC and RBC PC-species of patients with HbSC and HbSS are related to RBC polyamines. Low RBC 18:2U6 is almost stoichiometrically compensated for by higher stearic and palmitic acids. Circulating RBC from patients with HbSC and HbSS have normal total polyunsaturated FA with 20 carbons or more. Low RBC 18:2U6 of patients with HbSS and HbSC is rather related to young RBC-age (RBC polyamines) than to diet (plasma CE-FA). Their rapid RBC turnover causes incomplete RBC-FA exchange with plasma species (AU)

Screening of cord blood for haemoglobinopathies and thalassaemia by high-performance liquid chromatography - abstract

A high-performance liquid chromatography (HPLC) method for the screening of haemoglobins in cord blood was evaluated and the gene frequencies of the structural haemoglobin variants HbS and HbC and the synthesis variants O- and á+ -thalassaemia were studied in babies born on the Caribbean island of Curacao, the Netherlands Antilles. In 3 months, 67.2 percent of all (748) newborns were screened and 122 (24.3 percent) had an abnormal haemoglobin pattern, of which 53 (43.4 percent) had a haemoglobinopathy (HbS or HbC), 64(52.2 percent) O-thalassaemia (Hb Barts > 0.5 percent, corresponding with heterozygous or homozygous O-thalassaemia-2) and 5 (4.1 percent) a haemoglobinopathy plus O-thalassaemia. None of the newborns with heterozygous HbS and HbC had concomitant á+-thalassaemia. The population genotype frequency of heterozygous O-thalassaemia -2 remain undetected. The data are in excellent agreement with comparable published results. The HPLC method proved pre-eminently suitable for the screening of cord blood samples. (AU)