Clinical, biochemical and genetic spectrum of low alkaline phosphatase levels in adults.

BACKGROUND: Low serum levels of alkaline phosphatase (ALP) are a hallmark of hypophosphatasia. However, the clinical significance and the underlying genetics of low ALP in unselected populations are unclear. METHODS: In order to clarify this issue, we performed a clinical, biochemical and genetic study of 42 individuals (age range 20-77yr) with unexplained low ALP levels. RESULTS: Nine had mild hyperphosphatemia and three had mild hypercalcemia. ALP levels were inversely correlated with serum calcium (r=-0.38, p=0.012), pyridoxal phosphate (PLP; r=-0.51, p=0.001) and urine phosphoethanolamine (PEA; r=-0.49, p=0.001). Although many subjects experienced minor complaints, such as mild musculoskeletal pain, none had major health problems. Mutations in ALPL were found in 21 subjects (50%), including six novel mutations. All but one, were heterozygous mutations. Missense mutations were the most common (present in 18 subjects; 86%) and the majority were predicted to have a damaging effect on protein activity. The presence of a mutated allele was associated with tooth loss (48% versus 12%; p=0.04), slightly lower levels of serum ALP (p=0.002), higher levels of PLP (p<0.0001) and PEA (p<0.0001), as well as mildly increased serum phosphate (p=0.03). Ten individuals (24%) had PLP levels above the reference range; all carried a mutated allele. CONCLUSION: One-half of adult individuals with unexplained low serum ALP carried an ALPL mutation. Although the associated clinical manifestations are usually mild, in approximately 50% of the cases, enzyme activity is low enough to cause substrate accumulation and may predispose to defects in calcified tissues.

Estimated Glomerular Filtration Rate in Renal Transplantation: The Nephrologist in the Mist.

BACKGROUND: Formulas do not estimate renal function with acceptable precision and accuracy. METHODS: We compared 51 creatinine-based and/or cystatin c-based formulas with a gold standard (iohexol plasma clearance) in 193 renal transplant recipients using concordance correlation coefficient, total deviation index, coverage probability and the error in chronic kidney disease (CKD) stage classification. RESULTS: No formula showed a concordance correlation coefficient greater than 0.90 (average for creatinine-based formulas: ∼0.70 and for cystatin c-based formulas: ∼0.85). A wide total deviation index was observed: approximately 70% (creatinine-based) and approximately 50% (cystatin c-based), indicating that 90% of the estimations showed bounds of error of ±70% or ±50%, respectively, compared with the gold standard. No formula included 90% of the estimations within a coverage probability of ±10%. Half the CKD stages classified by creatinine-based formulas were incorrect, mainly due to overestimation of renal function. One of 3 CKD stages diagnosed by cystatin c-based formulas was incorrect, with both overestimation and underestimation. Overall, the formulas showed very low precision and accuracy and a high degree of error in reflecting real renal function. CONCLUSIONS: In conclusion, formulas do not properly reflect renal function in kidney transplantation, which makes their use in clinical practice unreliable. Moreover, their use in clinical trials should be avoided.

Influencia de la inflamación y la presencia de amiloide sobre el metabolismo lipídico en pacientes con artritis reumatoide / No disponible

Introducción Los pacientes con artritis reumatoide (AR) presentan una aterosclerosis acelerada, que se ha relacionado en parte con alteraciones del metabolismo lipídico asociadas al proceso inflamatorio, que incluye a la proteína sérica amiloide A. Objetivo Evaluar el perfil lipídico en pacientes con AR tratada y su relación con la actividad inflamatoria y la presencia de amiloidosis secundaria. Métodos Se estudiaron 78 pacientes mujeres con AR. A todas se les realizó una extracción sanguínea para analizar el perfil lipídico (colesterol total, c-HDL, c-HDL3, c-HDL2, c-LDL, triglicéridos, lipoproteína(a) y (..) (AU)

Introduction Patients with rheumatoid arthritis (RA) display an accelerated atherosclerosis that is related in part to lipid metabolism disorders associated with the inflammatory process, which includes serum amyloid protein A. Objective To evaluate the lipid profile in treated RA patients and its relationship to inflammatory activity and the presence of secondary amyloidosis.

Markers of inflammation before and during peritoneal dialysis.

In this study, we compared changes in inflammatory markers-C-reactive protein (CRP), pentraxin 3 (PTX3), serum component of amyloid A (SAA), and procalcitonin (PCT)-in 182 subjects: 69 from the general population (GP), 47 with CKD, 19 with an implanted intra-abdominal catheter for peritoneal dialysis ("prePD"), and 47 on peritoneal dialysis (PD). These were the results [median (95% confidence interval)] for the GP CKD, prePD, and PD groups respectively: CRP: 1.40 mg/L (1.15-2.10 mg/L), 5.30 mg/L (3.04-8.06 mg/L), 3.33 mg/L (2.15-12.58 mg/L), 7.25 mg/L (4.43-15.16 mg/L). SAA: 3.10 mg/L (2.90-3.53 mg/L), 7.77 mg/L (4.17-15.83 mg/L), 7.30 mg/L (4.81-10.96 mg/L), 9.14 mg/L (5.31-23.54 mg/L). PCT: 0.028 ng/mL (0.022-0.032 ng/mL), 0.121 ng/mL (0.094-0.166 ng/mL), 0.160 ng/mL (0.090-0.277 ng/mL), 0.363 ng/mL (0.222-0.481 ng/mL). PTX3: 0.54 ng/mL (0.33-0.62 ng/mL), 0.71 ng/ mL (0.32-1.50 ng/mL), 0.56 ng/mL (0.44-1.00 ng/ mL), 1.04 ng/mL (0.65-1.56 ng/mL). After catheter insertion, CRP showed a nonsignificant declining trend that disappeared throughout PD. The behavior of SAA was similar to that of CRP and was not modified by the changes induced by the start of PD. An increase in PTX3 was observed only with PD, which may be related to a local proinflammatory state caused by PD solution. We can conclude that catheter insertion for PD does not account for most of the local inflammatory changes observed in PD patients.

Inflammation markers, chronic kidney disease, and renal replacement therapy.

Chronic kidney disease (CKD) is associated with a proinflammatory state and an excess of cardiovascular risk. In this work, we describe changes in inflammatory markers-C-reactive protein (CRP), pentraxin 3 (PTX3), serum component of amyloid A (SAA), and procalcitonin (PCT)--in CKD patients compared with a control group of subjects with a normal estimated glomerular filtration rate (eGFR). Blood samples were obtained from 69 healthy individuals (GP) and 70 end-stage CKD patients--25 not yet on dialysis, 22 on peritoneal dialysis (PD), and 23 on hemodialysis (HD). These were the results [median (95% confidence interval)] for the GP CKD, PD, and HD groups respectively: CRP: 1.40 mg/L (1.19-2.11 mg/L), 6.50 mg/L (3.57-8.32mg/L), 7.60 mg/L (2.19-22.10mg/L), 9.60 mg/L (6.62-16.38 mg/L). SAA: 3.10 mg/L (2.90-3.53 mg/L), 7.11 mg/L (3.81-15.40mg/L), 9.69 mg/L (5.07-29.47mg/L), 15.90 mg/L (6.80-37.48 mg/L). PCT: 0.03 ng/mL (0.02-0.03 ng/mL), 0.12 ng/mL (0.09-0.16 ng/mL), 0.32 ng/mL (0.20-0.46 ng/ mL), 0.79 ng/mL (0.45-0.99 ng/mL). PTX3: 0.54 ng/mL (0.33-0.62 ng/mL), 0.71 ng/ mL (0.32-1.50 ng/mL), 1.52 ng/mL (0.65-2.13 ng/mL), 1.67 ng/mL (1.05-2.27 ng/mL). Compared with levels in the GP group, levels of SAA and CRP (systemic response) were significantly higher in CKD patients on and not on dialysis. Levels of PTX3 were higher only in dialyzed patients, significantly so in those on HD (greatly different from the CRP levels). These differing levels might be related to a local reaction caused by an invasive intervention (PD or HD). As eGFR declines and with the start of renal replacement therapy, PCT increases. Levels of PCT could potentially cause confusion when these patients are being evaluated for the presence of infection, and may also demonstrate some microvascular implications of dialysis therapy.

Factores de riesgo emergentes / Emergent risk factors

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Causas principales de mortalidad precoz y exceso de mortalidad en la población diabética española. Estudio DRECE III / No disponible

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Conventional lipid profile and lipoprotein(a) concentrations in treated patients with rheumatoid arthritis.

OBJECTIVE: Patients with rheumatoid arthritis (RA) have an increased cardiovascular risk not completely explained by traditional cardiovascular risk factors. If the proatherogenic lipid profile observed in active and untreated RA improves by effectively treating RA without the use of a lipid-lowering agent, other nonconventional cardiovascular lipid risk factors may be implicated. We evaluated conventional lipid risk factors and lipoprotein(a) in treated patients with RA. METHODS: This cross-sectional study was conducted in 122 patients with RA. Lipid profiles of patients were compared with a control group, consisting of a population-based study cohort (DRECE study), matched for sex, age, menopausal status, and body mass index. Excess lipoprotein(a) was defined by a serum concentration > 0.3 g/l. RESULTS: High-density lipoprotein cholesterol (HDL-c) concentrations were higher in pre- and postmenopausal women with RA than in controls (p = 0.023 and p

Sodium bicarbonated mineral water decreases postprandial lipaemia in postmenopausal women compared to a low mineral water.

The role of bicarbonated mineral waters on lipid metabolism and lipoprotein concentrations in man has scarcely been investigated. The present study aimed to investigate whether drinking sodium bicarbonated mineral water affects postprandial cholesterol and triacylglycerol metabolism in postmenopausal women. In a three-way, randomised, crossover study, eighteen healthy postmenopausal women consumed two sodium bicarbonated mineral waters (bicarbonated mineral water 1 and bicarbonated mineral water 2) and a low mineral water (500 ml of each) with a standard fat-rich meal (4552 kJ; 75.3 g fat). The bicarbonated waters were rich in sodium and bicarbonate and bicarbonated mineral water 1 contained 5.7 times more fluoride than bicarbonated mineral water 2. Fasting blood samples and postprandial blood samples were taken at 30, 60, 120, 240, 360 and 420 min after the end of the meal consumption. Cholesterol and triacylglycerols were determined in serum and chylomicrons. A significant water consumption effect was observed in the total area under the curve (TAUC) of serum and chylomicron triacylglycerols (ANOVA, P=0.008 and P=0.027, respectively). TAUC of serum triacylglycerols for bicarbonated mineral water 2 was significantly lower compared to low mineral water (Bonferroni, P=0.039). Peak concentration of serum triacylglycerols showed a significant water effect (P=0.025). Changes in chylomicron cholesterol were not significantly affected by the type of water. Bicarbonated mineral waters 1 and 2 did not show any significant differences. Drinking sodium bicarbonate-rich mineral waters reduces postprandial lipaemia in healthy postmenopausal women compared to drinking a low mineral water.

A sodium-rich carbonated mineral water reduces cardiovascular risk in postmenopausal women.

This study was designed to investigate the possible beneficial effects of consuming a sodium-rich carbonated mineral water on lipoprotein metabolism and to determine whether consumption of this water influences endothelial dysfunction (ED) in postmenopausal women. Women included in the study were amenorrheic (>1 y), healthy, and not obese (BMI < 30 kg/m(2)). The subjects did not take estrogen replacement therapy; supplements of vitamins, minerals, and phytoestrogens; or other medications known to affect bone and lipid metabolism. The study consisted of 2 intervention periods of 2 mo each, during which women drank 1 L/d of a control mineral water (low mineral content) for 2 mo followed by the carbonated mineral water, rich in sodium, bicarbonate, and chloride, for 2 mo. Body weight, height, and blood pressure were measured, and BMI was calculated. Blood samples were taken from fasting subjects and serum was analyzed for total cholesterol, HDL-cholesterol, LDL-cholesterol, triacylglycerols, apolipoprotein AI, apolipoprotein B, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and glucose. Blood pressure levels did not change throughout the study. Carbonated water intake decreased total cholesterol and LDL-cholesterol levels by 6.8% (P = 0.001) and 14.8% (P < 0.0001), respectively, whereas HDL-cholesterol concentration increased by 8.7% (P = 0.018), compared to the control period. Therefore, cardiovascular disease (CVD) risk indexes (total cholesterol/HDL-cholesterol and LDL-cholesterol/HDL-cholesterol) were markedly reduced (both P < 0.0001). Soluble ICAM-1 and sVCAM-1 levels decreased by 8.4% (P = 0.007) and 14.8% (P = 0.015), respectively. Fasting serum glucose concentration decreased by 6.7% (P < 0.0001). Triacylglycerol levels did not change. Consumption of this sodium rich carbonated water can play a beneficial role in the prevention of CVD and the metabolic syndrome.

Central adiposity determines prevalence differences of the metabolic syndrome.

OBJECTIVE: To compare the expression of the metabolic syndrome in Spain and San Antonio, TX, two populations with major differences regarding their cardiovascular risk profile. RESEARCH METHODS AND PROCEDURES: Cross-sectional analysis of population-based, epidemiological surveys using the metabolic syndrome definition of the National Cholesterol Education Program. In San Antonio, we limited our analysis to non-Hispanic whites because non-Hispanic whites are largely of European ancestry (n = 1339 in San Antonio and 2947 in Spain) RESULTS: In men, increased central adiposity was more prevalent in San Antonio than in Spain (29.7 vs. 23.0%, p < 0.0001); in women, it was less prevalent in San Antonio than in Spain (40.2 vs. 66.4%, p < 0.0001). The metabolic syndrome followed that same pattern: more prevalent in men (28.9 vs. 20.8%, p = 0.019) and less in women from San Antonio (27.1 vs. 30.9%, p < 0.0001). In subjects with the metabolic syndrome, most women had increased central adiposity (92.6% in San Antonio and 97.5% in Spain), and most men had either increased central adiposity or blood pressure (99.2% in San Antonio and 95.0% in Spain). DISCUSSION: Contrary to men, the metabolic syndrome is more prevalent in Spanish women than in women from San Antonio with differences that mirror differences in central adiposity. Central adiposity and blood pressure may be used to exclude the metabolic syndrome. Considering recent secular trends in obesity, we predict there will be an increase in the prevalence of the metabolic syndrome in both populations in the coming years.

A six-month, multicenter, open-label, noncomparative, prospective, observational study of the efficacy and tolerability of atorvastatin in the primary care setting(estudio del control de las hiperlipidemiasen atención primaria): the cheap study.

BACKGROUND: A close relationship exists between high levels of total cholesterol (TC) (particularly low-density lipoprotein cholesterol [LDL-C]) and low levels of high-density lipoprotein cholesterol (HDL-C), which is associated with an increased risk for arteriosclerosis and cardiovascular disease (CVD). Evidence shows that atorvastatin produces significantly greater reductions in LDL-C and TC than other hydroxymethylglutaryl-coenzyme A reductase inhibitors. However, the results achieved in clinical studies could be different from those found in general clinical practice, where patient follow-up is less thorough and poorer compliance may reduce the effectiveness of the lipid-lowering therapy. OBJECTIVE: The aim of this study was to assess the effectiveness of atorvastatin in achieving the LDL-C levels recommended by several Spanish scientific societies, as well as its tolerability in standard clinical use. METHODS: This 6-month, open-label, noncomparative, prospective, observational study was conducted in 1351 primary care centers in Spain. All patients were aged 18 to 80 years and had primary hypercholesterolemia (TC >200 mg/dL and triglycerides [TG] 200 mg/dL and fasting TG 200-400 mg/dL). All patients also had LDL-C levels higher than those established by the Spanish Society of Arteriosclerosis (Sociedad Española de Arteriosclerosis [SEA]) according to baseline cardiovascular risk and previous use of lipid-lowering therapy (for patients with low, moderate, or high cardiovascular risk, the recommended LDL-C goals are ≤175 mg/dL, ≤155 mg/dL, and ≤135 mg/dL, respectively; for patients with CVD, the LDL-C goal is ≤100 mg/dL). None of the patients had creatine kinase activity ≥540 U/L or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥60 U/L. Study visits occurred at months 0, 2, and 6 of treatment. Patients received atorvastatin calcium 10 mg/d for 2 months. The dosage was then doubled to 20 mg/d in patients who did not achieve the SEA LDL-C goal and also in those patients whose primary care physicians (PCPs) deemed this higher dosage necessary; this dosage was continued for at least 4 additional months, to complete at least a 6-month course of treatment. The percentage of patients who achieved their goals was used to measure atorvastatin effectiveness. Percentages of change in LDL-C, TC, TG, and HDL-C from baseline to the final study visit also were used as measures of effectiveness. The incidence of adverse events (AEs) per 10,000 patient-months was used for the primary tolerability analysis. A secondary tolerability analysis was performed in all patients treated with atorvastatin who had some recorded follow-up, regardless of whether the patient met inclusion criteria. Information was obtained from data recorded in the case-report forms. RESULTS: A total of 5317 outpatients (2715 women, 2598 men, 4 sex unknown; mean [SD] age, 58.7 [10.5] years) were enrolled. Among patients receiving known dosages of atorvastatin, 1580 of 4033 (39.2%) and 2378 of 3585 (66.3%) patients met the SEA LDL-C goal after 2 and 6 months of therapy, respectively (P

Effect of atorvastatin and bezafibrate on plasma levels of C-reactive protein in combined (mixed) hyperlipidemia.

C-reactive protein (CRP) is a non-specific but sensitive marker of underlying systemic inflammation. High CRP plasma levels correlate with risk for future cardiovascular events. The present study evaluated the effects of atorvastatin (10-40 mg) and bezafibrate (400 mg) on CRP concentrations after 6 and 12 months of treatment in 103 patients with combined (mixed) hyperlipidemia. The number of cardiovascular risk factors present in a given patient was associated with baseline CRP levels. After 6 months and 1 year, atorvastatin treatment was associated with significant (P<0.001) decreases from baseline of CRP concentrations by 29 and 43%, respectively, while bezafibrate-treated patients showed non-significant reductions of 2.3 and 14.6%, respectively (P=0.056 and 0.005 for the respective differences between the two treatment arms at 6 months and 1 year). The magnitude of change in CRP after 1 year was directly related to baseline CRP levels. Covariance analysis showed that CRP decreases in the atorvastatin group were unrelated to total cholesterol and LDL cholesterol reductions; however, they were directly related to triglyceride changes (r=0.28, P=0.047) and inversely related to HDL cholesterol changes (r=-0.28, P=0.045). A model including baseline CRP values and treatment effect showed that atorvastatin use was a significant predictor of change in CRP levels over time (beta=0.82, P=0.023). These results suggest a potential anti-atherosclerotic additional benefit of atorvastatin in patients at a risk of cardiovascular disease.