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N Rifai

Publications and source records attributed to N Rifai.

At least 55 records · Page 3Linked to original sources
PubMed2001

High sensitivity immunoassays for C-reactive protein: promises and pitfalls.

C-reactive protein (CRP) has historically been measured in the clinical laboratory for the detection and monitoring of occult infection and inflammation, using immunoturbidimetric or immunonephelometric techniques. The recent commercial availability of automated high-sensitivity assays has enabled investigators to measure CRP at levels previously unattainable on a routine basis and to explore its clinical utility in apparently healthy individuals. CRP concentrations increased above the individuals' baselines but still within the normal reference intervals have been observed in association with increasing age, obesity, and smoking and in individuals with chronic infections such as Chlamydia pneumoniae and Helicobacter pylori. More importantly, however, data from prospective studies have shown CRP to be a strong and independent predictor of future coronary events in subjects with and without coronary heart disease. An algorithm for risk assessment of coronary risk employing both CRP and lipid concentrations has recently been proposed. However, in order for this approach to be incorporated into clinical practice, agreement among the various CRP methods must be achieved. Of critical importance to this process is a basic understanding of issues affecting assay performance. Factors such as assay precision, sensitivity, matrix effects, calibration, and standardization need to be addressed adequately by the in vitro diagnostic industry and the clinical laboratory.

Algorithms↗
PubMed2001

Fasting plasma homocysteine levels in the insulin resistance syndrome: the Framingham offspring study.

OBJECTIVE: Insulin resistance, associated metabolic abnormalities, and elevated homocysteine levels are risk factors for cardiovascular disease (CVD). We examined relationships between homocysteine levels and features of insulin resistance syndrome (IRS). RESEARCH DESIGN AND METHODS: We measured clinical characteristics, plasma levels of fasting homocysteine, folate, B vitamins, creatinine, and fasting and 2-h insulin and glucose levels after a 75-g oral glucose tolerance test in 2,214 subjects without CVD at the fifth examination (1991-1995) of the Framingham Offspring Study. After excluding 203 subjects with diabetes, the remaining 2,011 subjects were categorized as having none, one, two, or all three of the phenotypes of IRS: impaired glucose tolerance, hypertension, and/or a central metabolic syndrome (two or more traits: obesity, dyslipidemia, or hyperinsulinemia). In addition, in 1,592 subjects attending the sixth examination (1995-1998), we measured the urine albumin/creatinine ratio (UACR). Age-, sex-, creatinine-, vitamin-, and UACR-adjusted mean homocysteine levels or proportions with homocysteine >14 micromol/l in each phenotypic category and differences between categories were assessed with regression models. RESULTS: The mean age of the subjects was 54 years (range 28-82); 55% were women, 12.3% had hyperinsulinemia, and 15.9% had two or more of the IRS phenotypes. Adjusted mean homocysteine levels were higher comparing those with hyperinsulinemia (9.8 micromol/l) and those without (9.4 micromol/l, P = 0.04) and were higher among subjects with two or more IRS phenotypes (9.9 micromol/l) compared with those with 1 or no phenotype (9.3 micromol/l, P = 0.003). Mean UACR levels were also higher among subjects with two or more IRS phenotypes (7.2 mg/g) compared with those with 1 or no phenotype (5.5 mg/g, P = 0.007). CONCLUSIONS: Hyperhomocysteinemia and abnormal urinary albumin excretion are both associated with hyperinsulinemia and may partially account for increased risk of CVD associated with insulin resistance. Because hyperhomocysteinemia and microalbuminuria also reflect endothelial injury, these observations also support the hypothesis that endothelial dysfunction is associated with expression of the IRS.

Adult↗
PubMed2001

High-sensitivity C-reactive protein: a novel and promising marker of coronary heart disease.

BACKGROUND: Coronary heart disease remains the leading cause of morbidity and mortality in the industrialized world. Clinical and laboratory studies have shown that inflammation plays a major role in the initiation, progression, and destabilization of atheromas. C-Reactive protein (CRP), an acute phase reactant that reflects low-grade systemic inflammation, has been studied in a variety of cardiovascular diseases. APPROACH: Findings from prospective clinical trials were examined to determine the prognostic utility of CRP in acute coronary syndromes, and observations from epidemiological studies were reviewed to determine the ability of CRP to predict future first coronary events. The analytical considerations of CRP measurement in these clinical applications were also examined. CONTENT: In patients with established coronary disease, CRP has been shown to predict adverse clinical events. In addition, prospective studies have consistently shown that CRP is a strong predictor of future coronary events in apparently healthy men and women. The relative risk associated with CRP is independent of other cardiovascular disease risk factors. High-sensitivity CRP (hs-CRP) assays are needed for risk assessment of cardiovascular disease. Such assays are currently available but may require further standardization because patients' results will be interpreted using population-based cutpoints. Preventive therapies to attenuate coronary risk in individuals with increased hs-CRP concentrations include aspirin and statin-type drugs. SUMMARY: hs-CRP has prognostic utility in patients with acute coronary syndromes and is a strong independent predictor of future coronary events in apparently healthy subjects.

Biomarkers↗
PubMed2001

Evaluation of nine automated high-sensitivity C-reactive protein methods: implications for clinical and epidemiological applications. Part 2.

BACKGROUND: C-Reactive protein (CRP) can provide prognostic information about risk of future coronary events in apparently healthy subjects. This application requires higher sensitivity assays than have traditionally been available in the clinical laboratory. METHODS: Nine high-sensitivity CRP (hs-CRP) methods from Dade Behring, Daiichi, Denka Seiken, Diagnostic Products Corporation, Iatron, Kamiya, Olympus, Roche, and Wako were evaluated for limit of detection, linearity, precision, prozone effect, and comparability with samples from 388 apparently healthy individuals. RESULTS: All methods had limits of detection that were lower than the manufacturers' claimed limit of quantification except for the Kamiya, Roche, and Wako methods. All methods were linear at 0.3-10 mg/L. The Diagnostic Products Corporation, Kamiya, Olympus, and Wako methods had imprecision (CVs) >10% at 0.15 mg/L. The Iatron, Olympus, and Wako methods demonstrated prozone effects at hs-CRP concentrations of 12, 206, and 117 mg/L, respectively. hs-CRP concentrations demarcating each quartile in a healthy population were method-dependent. Ninety-two to 95% of subjects were classified into the same quartile of hs-CRP established by the Dade Behring method by the Denka Seiken, Diagnostic Products Corporation, Iatron, and Wako methods. In contrast, 68-77% of subjects were classified into the same quartile by the Daiichi, Kamiya, Olympus, and Roche methods. No subject varied by more than one quartile by any method. CONCLUSIONS: Four of the nine examined hs-CRP methods classified apparently healthy subjects into quartiles of hs-CRP similar to the classifications assigned by the comparison method. Additional standardization efforts are required because an individual patient's results will be interpreted using population-based cutpoints.

Adolescent↗
PubMed2001

Absence of diurnal variation of C-reactive protein concentrations in healthy human subjects.

BACKGROUND: The concentration of C-reactive protein (CRP) in otherwise healthy subjects has been shown to predict future risk of myocardial infarction and stroke. CRP is synthesized by the liver in response to interleukin-6, the serum concentration of which is subject to diurnal variation. METHODS: To examine the existence of a time-of-day effect for baseline CRP values, we determined CRP concentrations in hourly blood samples drawn from healthy subjects (10 males, 3 females; age range, 21-35 years) during a baseline day in a controlled environment (8 h of nighttime sleep). RESULTS: Overall CRP concentrations were low, with only three subjects having CRP concentrations >2 mg/L. Comparison of raw data showed stability of CRP concentrations throughout the 24 h studied. When compared with cutoff values of CRP quintile derived from population-based studies, misclassification of greater than one quintile did not occur as a result of diurnal variation in any of the subjects studied. Nonparametric ANOVA comparing different time points showed no significant differences for both raw and z-transformed data. Analysis for rhythmic diurnal variation using a method fitting a cosine curve to the group data was negative. CONCLUSIONS: Our data show that baseline CRP concentrations are not subject to time-of-day variation and thus help to explain why CRP concentrations are a better predictor of vascular risk than interleukin-6. Determination of CRP for cardiovascular risk prediction may be performed without concern for diurnal variation.

Adult↗
PubMed2001

Variability and classification accuracy of serial high-sensitivity C-reactive protein measurements in healthy adults.

BACKGROUND: Increased concentrations of high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation, are associated with increased risk for coronary heart disease. Because of its relationship to inflammation, hs-CRP has considerable biologic variation. This study was carried out to characterize CRP variation and to compare it to another risk factor, total serum cholesterol. METHODS: One hundred thirteen individuals were scheduled to have five measurements each of hs-CRP and total cholesterol carried out at quarterly intervals over a 1-year period. Variations of hs-CRP and total cholesterol were characterized, and classification accuracy was described and compared for both. RESULTS: The relative variation was comparable for hs-CRP and total cholesterol. When classified by quartile, 63% of first and second hs-CRP measurements were in agreement; for total cholesterol it was 60%. Ninety percent of hs-CRP measurements were within one quartile of each other. This relationship was not altered by the use of log-transformed hs-CRP data. CONCLUSION: hs-CRP has a degree of measurement stability that is similar to that of total cholesterol.

Adult↗
PubMed2001

Evolution of methods for measurement of HDL-cholesterol: from ultracentrifugation to homogeneous assays.

BACKGROUND: Adoption of automated homogeneous assays for HDL-cholesterol (HDL-C) is increasing, driven by the need of clinical laboratories to cope with increasing workloads while containing costs. However, performance characteristics of homogeneous assays often differ in important aspects from those of the earlier precipitation methods. This review provides an overview of the new generation of homogeneous assays for HDL-C within the historical context of the evolution of methods and the efforts to standardize measurements of the lipoproteins. APPROACH: This is a narrative review based on method evaluations conducted in the laboratories of the authors as well as on relevant publications, especially comparative evaluation studies, from the literature. Publications considered here have been collected by the authors over the past 30 years of involvement as methods for HDL-C made the transition from their early use in lipid research laboratories to clinical laboratories and the recent emergence of homogeneous assays. CONTENT: The presentation includes descriptions of methodologies, including homogeneous, precipitation, electrophoresis, and ultracentrifugation assays. Reference methods and recommended approaches for assessing accuracy are described. Accuracy and imprecision are summarized in the context of the National Cholesterol Education Program (NCEP) standards for analytical performance. The effects of interfering substances and preanalytical sources of variation are presented. SUMMARY: Homogeneous assays have been shown to be reasonably well suited for use in routine clinical laboratories, generally meeting the NCEP criteria for precision, accuracy, and total error. However, discrepant results compared with the reference methods have been observed with some of the assays, and the sources of discrepancies are not well characterized. Some homogeneous reagents have not been thoroughly evaluated. At least three of the reagents have experienced successive adjustments in formulation; hence, the reagents may not yet be fully optimized. For these reasons, the homogeneous assays cannot be confidently recommended for use in long-term clinical trials and other research applications without thorough validation.

Chemical Precipitation↗
PubMed2000

Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy.

OBJECTIVES: We sought to evaluate cardiac troponin I (cTnI) for predicting early clinical outcomes and the efficacy of enoxaparin among patients with non-ST segment elevation acute coronary syndrome (ACS) and negative creatine kinase, MB fraction (CK-MB) levels. BACKGROUND: Cardiac TnI identifies patients with unstable angina who are at higher risk of death or myocardial infarction (MI) by 30 days. The utility of cTnI for predicting very early clinical events, including recurrent ischemia, and the efficacy of enoxaparin are not yet established. METHODS: At baseline and 12 h to 24 h after enrollment in the Thrombolysis in Myocardial Infarction (TIMI)-11B trial, samples were collected for cTnI determination. RESULTS: Among 359 patients with negative serial CK-MB values, 50.1% had a cTnI result > or =0.1 ng/ml within the first 24 h. Patients with elevated cTnI were at higher risk of death or MI at 48 h (3.9 vs. 0%, p = 0.01) and 14 days (13.9 vs. 2.2%, p<0.0001). Elevated cTnI also correlated with higher risk of recurrent ischemia requiring urgent revascularization by 48 h (10.0 vs. 1.7%, p = 0.001) and 14 days (20.6 vs. 5.6%, p< or =0.0001). Enoxaparin had a greater benefit among patients with elevated vs. normal cTnI (p = 0.03), achieving a 47% reduction in the risk of death, MI or urgent revascularization by 14 days in cTnI-positive patients (p = 0.007). CONCLUSIONS: Elevation of cTnI among patients with non-ST segment elevation ACS and negative levels of CK-MB identifies those at higher risk for very early adverse outcomes, including severe recurrent ischemia. Treatment with enoxaparin reduces the risk associated with elevated cTnI.

Aged↗
PubMed2000

Effects of growth hormone administration on inflammatory and other cardiovascular risk markers in men with growth hormone deficiency. A randomized, controlled clinical trial.

BACKGROUND: Growth hormone-deficient adults have increased cardiovascular mortality. Growth hormone replacement may affect cardiovascular risk. Inflammation plays an important role in atherosclerosis, and inflammatory markers are predictive of cardiovascular events. OBJECTIVE: To investigate the effect of growth hormone replacement on inflammatory and other cardiovascular risk factors. DESIGN: Randomized, single-blind, placebo-controlled trial. PATIENTS: 40 men with adult-onset growth hormone deficiency. INTERVENTION: Growth hormone or placebo given for 18 months at a dose adjusted for normal serum insulin-like growth factor I level. MEASUREMENTS: Anthropometric, hemoglobin A1c, and central fat values were assessed every 6 months. Levels of glucose, insulin, insulin-like growth factor I, and lipids were measured at 1, 3, 6, 12, and 18 months. C-reactive protein, serum amyloid polypeptide A, inteleukin-6, and lipoprotein(a) levels were determined at baseline and 6 and 18 months. RESULTS: C-reactive protein and inteleukin-6 levels decreased in growth hormone recipients compared with placebo recipients (differences between groups, -1.9 +/- 0.6 mg/L [P = 0.0027] and -1.3 +/- 0.5 ng/L [P = 0.013], respectively). Changes in serum amyloid polypeptide A levels between groups did not reach statistical significance (difference between groups, -2.4 +/- 1.2 mg/L; P = 0.056). Serum cholesterol levels, low-density lipoprotein cholesterol levels, and ratios of total cholesterol to high-density lipoprotein cholesterol decreased in growth hormone recipients in the first 3 months compared with placebo recipients (differences between groups, -0.86 +/- 0.17 mmol/L [-33.2 +/- 6.6 mg/dL] [P < 0.001], -0.63 +/- 0.20 mmol/L [-24.5 +/- 5.9 mg/dL] [P < 0.001], and -0.56 +/- 0.26 [P = 0.040], respectively), but the decrease was not maintained from month 6 to month 18. Lipoprotein(a) levels increased (difference between groups, 22.0 +/- 8.0 mg/L; P = 0.0096). Short-term increases occurred in glucose levels, insulin levels, and insulin-to-glucose ratios (differences between groups, 0.54 +/- 0.16 mmol/L [9.6 +/- 2.8 mg/dL] [P = 0.0018], 37.9 +/- 9.6 pmol/L [P < 0.001], and 6.0 +/- 1.8 [P = 0.0025], respectively), but only the increase in glucose level was maintained over the long term (difference between groups, 0.56 +/- 0.17 mmol/L [10.0 +/- 3.1 mg/dL]; P = 0.0026). Hemoglobin A1c values did not change. Truncal fat-to-total fat ratios decreased (difference between groups, -0.018 +/- 0.007; P = 0.0087). CONCLUSIONS: Long-term growth hormone replacement in men reduces levels of inflammatory cardiovascular risk markers, decreases central fat, and increases lipoprotein(a) and glucose levels without affecting lipid levels.

Adipose Tissue↗
PubMed2000

Elevation of tumor necrosis factor-alpha and increased risk of recurrent coronary events after myocardial infarction.

BACKGROUND: Levels of tumor necrosis factor-alpha (TNF-alpha) increase with acute ischemia. However, whether elevations of TNF-alpha in the stable phase after myocardial ischemia (MI) are associated with increased risk of recurrent coronary events is unknown. METHODS AND RESULTS: A nested case-control design was used to compare TNF-alpha levels obtained an average of 8.9 months after initial MI among 272 participants in the Cholesterol And Recurrent Events (CARE) trial who subsequently developed recurrent nonfatal MI or a fatal cardiovascular event (cases) and from an equal number of age- and sex-matched participants who remained free of these events during follow-up (controls). Overall, TNF-alpha levels were significantly higher among cases than controls (2.84 versus 2.57 pg/mL, P=0.02). The excess risk of recurrent coronary events after MI was predominantly seen among those with the highest levels of TNF-alpha, such that those with levels in excess of 4.17 pg/mL (the 95th percentile of the control distribution) had an approximately 3-fold increase in risk (RR=2.7, 95% CI 1.4 to 5.2, P=0.004). Risk estimates were independent of other risk factors and were similar in subgroup analyses limited to cardiovascular death (RR=2.1) or to recurrent nonfatal MI (RR=3.2). CONCLUSIONS: Plasma concentrations of TNF-alpha are persistently elevated among post-MI patients at increased risk for recurrent coronary events. These data support the hypothesis that a persistent inflammatory instability is present among stable patients at increased vascular risk. Novel therapies designed to attenuate inflammation may thus represent a new direction in the treatment of MI.

Adult↗
PubMed2000

Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men.

BACKGROUND: Interleukin-6 (IL-6) plays a central role in inflammation and tissue injury. However, epidemiological data evaluating the role of IL-6 in atherogenesis are sparse. METHODS AND RESULTS: In a prospective study involving 14 916 apparently healthy men, we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infarction (MI) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up. Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not (1.81 versus 1. 46 pg/mL; P=0.002). The risk of future MI increased with increasing quartiles of baseline IL-6 concentration (P for trend <0.001) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile (95% CI 1.3 to 4.3, P=0.005); for each quartile increase in IL-6, there was a 38% increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors, was stable over long periods of follow-up, and was present in all low-risk subgroups, including nonsmokers. Although the strongest correlate of IL-6 in these data was C-reactive protein (r=0.43, P<0.001), the relationship of IL-6 with subsequent risk remained after control for this factor (P<0.001). CONCLUSIONS: In apparently healthy men, elevated levels of IL-6 are associated with increased risk of future MI. These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis.

C-Reactive Protein↗
PubMed2000

C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.

BACKGROUND: Since inflammation is believed to have a role in the pathogenesis of cardiovascular events, measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events. METHODS: We conducted a prospective, nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation. The markers included high-sensitivity C-reactive protein (hs-CRP), serum amyloid A, interleukin-6, and soluble intercellular adhesion molecule type 1 (sICAM-1). We also studied homocysteine and a variety of lipid and lipoprotein measurements. Cardiovascular events were defined as death from coronary heart disease, nonfatal myocardial infarction or stroke, or the need for coronary-revascularization procedures. RESULTS: Of the 12 markers measured, hs-CRP was the strongest univariate predictor of the risk of cardiovascular events; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 (95 percent confidence interval, 2.2 to 8.9). Other markers significantly associated with the risk of cardiovascular events were serum amyloid A (relative risk for the highest as compared with the lowest quartile, 3.0), sICAM-1 (2.6), interleukin-6 (2.2), homocysteine (2.0), total cholesterol (2.4), LDL cholesterol (2.4), apolipoprotein B-100 (3.4), HDL cholesterol (0.3), and the ratio of total cholesterol to HDL cholesterol (3.4). Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone (P<0.001). The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter (3.4 mmol per liter), the target for primary prevention established by the National Cholesterol Education Program. In multivariate analyses, the only plasma markers that independently predicted risk were hs-CRP (relative risk for the highest as compared with the lowest quartile, 1.5; 95 percent confidence interval, 1.1 to 2.1) and the ratio of total cholesterol to HDL cholesterol (relative risk, 1.4; 95 percent confidence interval, 1.1 to 1.9). CONCLUSIONS: The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events.

Analysis of Variance↗
PubMed2000

Heart-type fatty acid binding protein as a marker of reperfusion after thrombolytic therapy.

Accurate, rapid, and simple noninvasive measures of infarct-related artery (IRA) patency are needed to identify patients with failed coronary reperfusion for rescue percutaneous coronary intervention (PCI). Heart-type Fatty Acid Binding Protein (H-FABP) is a small, cytosolic protein found in high concentrations in the myocardium. We evaluated the efficacy of H-FABP as a marker for successful reperfusion after thrombolysis. Fifty-eight subjects from the TIMI 14 trial had H-FABP and myoglobin concentrations measured at baseline (immediately prior to thrombolysis) and 60, 90, and 180 min after thrombolysis. All patients underwent coronary angiography at 90 min. By 60 min after thrombolysis, median concentrations of H-FABP and myoglobin were significantly higher in patients with a patent IRA than in those with an occluded IRA (P<0.01 for each). Similarly, the 60 and 90 min/baseline H-FABP and myoglobin ratios were significantly higher among patients with a patent IRA (P<0.01 for each). There were no significant differences in marker concentrations or ratios between patients with TIMI grade 2 and TIMI grade 3 flow. The area under the ROC curve tended to be greater for the 60 and 90 min/baseline myoglobin ratios than for similar ratios of H-FABP (0.71 and 0.73 vs. 0.64 and 0.62; P=ns). In conclusion, successful reperfusion can be detected within the first 60 min after thrombolysis with either H-FABP or myoglobin. Despite a favorable kinetic profile, however, H-FABP does not appear to represent a significant advance over myoglobin in the noninvasive detection of reperfusion after thrombolysis.

Biomarkers↗
PubMed2000

Analytical performance and clinical efficacy of three routine procedures for LDL cholesterol measurement compared with the ultracentrifugation-dextran sulfate-Mg(2+) method.

The diagnosis and management of adults with hypercholesterolemia in the US are largely based on low-density lipoprotein cholesterol (LDL-C) concentration. In order to classify someone correctly into the National Cholesterol Education Program cut-points, LDL-C must be measured with a total error of </=12%. We examined simultaneously the analytical and clinical performance of two homogeneous LDL-C assays (LDL-C(RD), Roche Diagnostics and LDL-C(GZ), Genzyme) and the Friedewald calculation (LDL-C(Fried)). These assays correlated highly with the ultracentrifugation-dextran sulfate-Mg(2+) method (LDL-C(RD): r=0.962, y=1.029x-0.48 mmol/l, n=134; LDL-C(GZ): r=0.961, y=0.986x-0.12 mmol/l, n=134; LDL-C(Fried): r=0.960, y=1.017x-0.18 mmol/l, n=115). The total error requirement was met by the LDL-C(GZ) assay at all clinical decision cut-points, whereas the LDL-C(RD) assay met this requirement only at LDL-C concentrations of 4.92 mmol/l. The LDL-C(Fried) failed to meet the total error requirement, because the compounded imprecision of the three independent tests required for this calculation was high. Both, the LDL-C(GZ) and the LDL-C(RD) assays appeared to be only slightly affected by increasing triglycerides. At the medical decision cut-point range, the LDL-C(RD), LDL-C(GZ) and LDL-C(Fried) assays showed positive predictive values of 89-100, 85-100 and 83-99%, respectively, and negative predictive values of 52-98, 77-98 and 68-98%, respectively. The homogeneous assays provide clinical laboratories with the means to measure LDL-C in hypertriglyceridemic samples and could have a role in the diagnosis and management of hyperlipidemic patients.

Adult↗
PubMed2000

Direct measurement of LDL-C in children: performance of two surfactant-based methods in a general pediatric population.

OBJECTIVES: Several pediatric advisory groups have recommended selective screening for dyslipidemia in children. Low-density lipoprotein cholesterol (LDL-C) is measured clinically with the Friedewald calculation in fasting samples. Nonfasting measurement of LDL-C would be clinically useful in children. DESIGN AND METHODS: In the present study, we examine the performance of two surfactant-based direct LDL-C assays in paired samples, fasting and nonfasting, from 100 children. RESULTS: LDL-C in the fasting state was significantly lower with the Friedewald estimation: 2.43 +/- 0. 61 mmol/L, N-geneous (Genzyme Corp.) direct LDL-C: 2.30 +/- 0.59 mmol/L, and Roche (Roche Diagnostics) direct LDL-C: 2.32 +/- 0.57 mmol/L than with ultracentrifugation-dextran-sulfate-Mg(2+) precipitation (UC-DS): 2.47 +/- 0.64 mmol/L. Moreover, there was increased negative bias using nonfasting samples with N-geneous: 2. 25 +/- 0.56 mmol/L and Roche: 2.26 +/- 0.56 mmol/L compared with fasting UC-DS. Correlation with US-DS was highest for Friedewald (r = 0.974) and fasting N-geneous (r = 0.973), and lowest with nonfasting N-geneous (r = 0.849) and Roche in fasting (r = 0.891) and nonfasting samples (r = 0.747). The sensitivity at LDL-C concentration of 2.85 mmol/L for the two direct methods when either fasting or nonfasting samples were used, was lower than that obtained with Friedewald. CONCLUSION: Overall, these direct LDL-C assays demonstrated limited utility in screening children but may be useful in the management of lipid disorders.

Autoanalysis↗
PubMed2000

High-sensitivity C-reactive protein and atherosclerosis: from theory to therapy.

Atherosclerosis remains the leading cause of morbidity and mortality in Western countries. Recent evidence has demonstrated that atherosclerosis is not simply a disease of lipid deposition. Inflammation plays a major role in the initiation, progression, and destabilization of atheromas. High-sensitivity C-reactive protein (hs-CRP) is a circulating acute-phase reactant that reflects active systemic inflammation. Large prospective trials have shown hs-CRP to be a strong predictor of future cardiovascular events. Increased hs-CRP concentration is in fact associated with higher cardiovascular events in individuals with and without clinical evidence of atherosclerotic disease. The relative risk associated with hs-CRP is independent of other cardiovascular disease risk factors. Assays for hs-CRP measurement are currently available but must be standardized because patients' results will be interpreted by using population-based cutpoints. A risk-stratifying algorithm incorporating hs-CRP and total cholesterol to high-density lipoprotein cholesterol ratio has been proposed. Further research into the mechanisms and pharmacological treatment of vascular disease will provide novel management strategies in the very near future.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2000

Race and gender differences in cord blood lipoproteins.

Race and gender differences in lipoproteins and apolipoproteins have repeatedly been demonstrated in adults. The same disparities have been observed in children of different race and gender, implying that these differences may be influenced by genetic factors. To further explore this hypothesis, cord blood concentrations of both lipoproteins and apolipoproteins were examined in black and white neonates of both sexes. Results were controlled for the observed effects of gestational age and growth parameters. Similar patterns of lipoprotein differences to those observed in adults and children were also detected between black and white, and between male and female neonates. These findings support the concept that the aetiology of the difference in lipoprotein concentration observed between race and gender groups includes a significant genetic component.

Apolipoproteins↗