Search PubMed⌕ Search

Biomedical subjects

Nader Rifai

Publications and source records attributed to Nader Rifai.

At least 109 records · Page 6Linked to original sources
PubMed2003

Habitual dietary intake of n-3 and n-6 fatty acids in relation to inflammatory markers among US men and women.

BACKGROUND: Polyunsaturated fatty acid intake favorably affects chronic inflammatory-related diseases such as cardiovascular disease; however, high intake of n-6 fatty acids may attenuate the known beneficial effects of n-3 fatty acids. METHODS AND RESULTS: We investigated habitual dietary n-3 fatty acid intake and its interaction with n-6 fatty acids in relation to the plasma inflammatory markers C-reactive protein, interleukin 6, and soluble tumor necrosis factor receptors 1 and 2 (sTNF-R1 and R2) among 405 healthy men and 454 healthy women. After adjustment for other predictors of inflammation, intake of the n-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) was inversely associated with plasma levels of sTNF-R1 and sTNF-R2 (P=0.03 and P<0.001, respectively) and somewhat less so for C-reactive protein (P=0.08). n-3 alpha-linolenic acid and n-6 cis-linoleic acid were not significantly related to the inflammatory markers. We found little if any association between n-3 fatty acid (EPA+DHA) intake and tumor necrosis factor receptors among participants with low intake of n-6 but a strong inverse association among those with high n-6 intake (P=0.04 and 0.002 for interaction of n-3 with n-6 on sTNF-R1 and sTNF-R2, respectively). CONCLUSIONS: These results suggest that n-6 fatty acids do not inhibit the antiinflammatory effects of n-3 fatty acids and that the combination of both types of fatty acids is associated with the lowest levels of inflammation. The inhibition of inflammatory cytokines may be one possible mechanism for the observed beneficial effects of these fatty acids on chronic inflammatory-related diseases.

Adult↗
PubMed2003

D-dimer, inflammatory markers, and lower extremity functioning in patients with and without peripheral arterial disease.

BACKGROUND: We determined whether higher levels of D-dimer, C-reactive protein (CRP), fibrinogen, and serum amyloid A are associated independently with functional impairment in patients with and without peripheral arterial disease (PAD). METHODS AND RESULTS: Participants were 370 men and women with PAD (ankle brachial index <0.90) and 231 without PAD. Functional outcomes were 6-minute walk distance and 4-meter walking velocity. A summary performance score combined performance in walking speed, standing balance, and time for 5 repeated chair rises into an ordinal score ranging from 0 to 12 (12=best). Adjusting for age, sex, ankle brachial index, comorbidities, and other potential mediators and confounders, D-dimer levels were associated independently and inversely with performance on all 3 functional measures in the entire cohort and among patients with and without PAD, respectively. Adjusting for known and potential confounders, CRP levels were associated independently with 6-minute walk distance and the summary performance score among participants with PAD. No significant associations were observed between CRP and the functional measures among participants without PAD. Fibrinogen and SAA levels were not associated independently with the functional measures. CONCLUSIONS: Higher D-dimer levels are associated with poorer functioning among individuals with and without PAD. Higher CRP levels were associated with poorer 6-minute walk performance and a lower summary performance score among participants with PAD but not among those without PAD. Additional study is needed to determine whether D-dimer and CRP are involved in the pathophysiology of functional impairment or whether they are simply sensitive markers of the extent of systemic atherosclerosis.

Aged↗
PubMed2003

Insulin, proinsulin, proinsulin:insulin ratio, and the risk of developing type 2 diabetes mellitus in women.

PURPOSE: To assess the associations among baseline levels of fasting insulin and proinsulin, proinsulin:insulin ratio, and the development of type 2 diabetes mellitus in apparently healthy middle-aged women. METHODS: In a nested case-control study involving a nationwide cohort of 27,628 participants from the Women's Health Study, 126 women with diabetes diagnosed during a 4-year follow-up period were compared with 225 age-matched controls. Fasting insulin level and proinsulin:insulin ratio were assessed in quartiles, and proinsulin level was assessed in categories (< or =4.0 pmol/L, 4.01 to 6.99 pmol/L, > or =7.0 pmol/L). The risk of developing type 2 diabetes was determined using conditional logistic regression analysis that adjusted for body mass index and other diabetes risk factors. RESULTS: Baseline insulin and proinsulin levels and proinsulin:insulin ratios were significantly higher among cases than among controls. Women with elevated insulin levels in the highest as compared with the lowest quartile were more likely to develop diabetes (odds ratio [OR] = 5.6; 95% confidence interval [CI]: 1.8 to 17.6), as were women with elevated (> or =7.0 pmol/L vs. < or =4.0 pmol/L) proinsulin levels (OR = 16.4; 95% CI: 5.8 to 46.8) and women with proinsulin:insulin ratios in the highest quartile (OR = 9.6; 95% CI: 3.1 to 30.8). Similar results were observed among women with a baseline hemoglobin A(1c) level < or =6.0%. In time-trend analyses, fasting insulin was a consistent predictor of long-term risk. Proinsulin and proinsulin:insulin ratio, although predictive throughout the study, were especially strong predictors of rapid progression to type 2 diabetes. CONCLUSION: Elevated fasting insulin and proinsulin levels and proinsulin:insulin ratio are associated with an increased risk of developing type 2 diabetes in apparently healthy middle-aged women.

Biomarkers↗
PubMed2003

C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14 719 initially healthy American women.

BACKGROUND: The metabolic syndrome describes a high-risk population having 3 or more of the following clinical characteristics: upper-body obesity, hypertriglyceridemia, low HDL, hypertension, and abnormal glucose. All of these attributes, however, are associated with increased levels of C-reactive protein (CRP). METHODS AND RESULTS: We evaluated interrelationships between CRP, the metabolic syndrome, and incident cardiovascular events among 14 719 apparently healthy women who were followed up for an 8-year period for myocardial infarction, stroke, coronary revascularization, or cardiovascular death; 24% of the cohort had the metabolic syndrome at study entry. At baseline, median CRP levels for those with 0, 1, 2, 3, 4, or 5 characteristics of the metabolic syndrome were 0.68, 1.09, 1.93, 3.01, 3.88, and 5.75 mg/L, respectively (P(trend) <0.0001). Over the 8-year follow-up, cardiovascular event-free survival rates based on CRP levels above or below 3.0 mg/L were similar to survival rates based on having 3 or more characteristics of the metabolic syndrome. At all levels of severity of the metabolic syndrome, however, CRP added prognostic information on subsequent risk. For example, among those with the metabolic syndrome at study entry, age-adjusted incidence rates of future cardiovascular events were 3.4 and 5.9 per 1000 person-years of exposure for those with baseline CRP levels less than or greater than 3.0 mg/L, respectively. Additive effects for CRP were also observed for those with 4 or 5 characteristics of the metabolic syndrome. The use of different definitions of the metabolic syndrome had minimal impact on these findings. CONCLUSIONS: These prospective data suggest that measurement of CRP adds clinically important prognostic information to the metabolic syndrome.

Aged↗
PubMed2003

Effect of pravastatin on LDL particle concentration as determined by NMR spectroscopy: a substudy of a randomized placebo controlled trial.

AIM: Recent data suggests that LDL particle concentration, as determined by Nuclear Magnetic Resonance (NMR) spectroscopy, may be associated with cardiovascular risk. We sought to determine the effect of randomization to pravastatin therapy on LDL particle concentration-NMR, among a primary prevention population. METHODS AND RESULTS: LDL particle concentration-NMR, LDL size-NMR, and standard chemical lipid parameters were measured at baseline and after 12 weeks among 500 individuals without overt coronary disease randomly allocated to pravastatin 40mg (n=256) or placebo (n=244). Randomization to pravastatin therapy caused a 19% reduction in median LDL particle concentration-NMR at 12 weeks, as compared to a 4.2% increase among those randomized to placebo (P<0.001 for pravastatin group compared to placebo). Pravastatin therapy caused a median 24.9% reduction in LDL cholesterol measured chemically compared to a 0.9% increase in the placebo group (P<0.001). Pravastatin therapy did not cause a significant change in median LDL size-NMR (0.5% increase in pravastatin group vs 0.0% in placebo group; P=0.25). The change in LDL particle concentration with pravastatin correlated inversely with baseline LDL size (r=-0.24; P<0.001) such that the largest reduction in LDL particle concentration-NMR was among those with the smallest LDL size-NMR at baseline (median% change =21.4% for tertile 1 of LDL size, 19.9% for tertile 2, and 16.5% for tertile 3; P=0.03). In contrast, pravastatin-induced changes in LDL cholesterol did not correlate with baseline LDL size-NMR (r=-0.05; P=0.47). CONCLUSION: Among individuals without overt hyperlipidemia or known coronary artery disease, randomized allocation to pravastatin (40mg) therapy for 12 weeks caused a reduction in LDL particle concentration-NMR, the magnitude of which was dependent on baseline LDL size-NMR.

Anticholesteremic Agents↗
PubMed2003

Leisure-time physical activity and reduced plasma levels of obesity-related inflammatory markers.

OBJECTIVE: This study investigated the relationship between physical activity and the obesity-related inflammatory markers C-reactive protein, interleukin-6, and soluble tumor necrosis factor receptors (sTNF-Rs) 1 and 2. Furthermore, we examined the relationship between physical activity and insulin sensitivity (insulin, C-peptide, and hemoglobin A(1c) levels) and whether inflammatory markers mediate this association. RESEARCH METHODS AND PROCEDURES: Biomarkers were measured in 405 healthy men and 454 healthy women from two large ongoing prospective studies. Information about physical activity and other variables was assessed by questionnaires. RESULTS: After adjustment for other predictors of inflammation, physical activity was inversely associated with plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein (p = 0.07, p = 0.004, p = 0.04, and p = 0.009). After further adjustment for BMI and leptin, as a surrogate for fat mass, most of these associations were no longer significant. Physical activity was also inversely related to insulin and C-peptide levels (p = 0.008 and p < 0.001); however, in contrast to BMI and leptin, levels of inflammatory markers explained only very little of this inverse relationship. DISCUSSION: These results suggest that frequent physical activity is associated with lower systemic inflammation and improved insulin sensitivity. These associations can partially be explained by a lower degree of obesity in physically active subjects. Although inflammatory markers may mediate obesity-dependent effects of physical activity on inflammatory related diseases such as type 2 diabetes or coronary heart disease, our study suggests that they do not directly account for the beneficial effects of physical activity on insulin resistance.

Adult↗
PubMed2003

Alcohol consumption patterns and HbA1c, C-peptide and insulin concentrations in men.

OBJECTIVE: Observational studies support inverse associations between moderate alcohol consumption and fasting insulin concentrations, but the importance of drinking pattern on the effect of alcohol on insulin sensitivity has not been fully explored. We examined the relations of alcohol consumption patterns-including average daily consumption, frequency of consumption and drinking with meals-to fasting insulin, fasting c-peptide and hemoglobin A1c (HbA1c). METHODS: A cross-sectional study of 462 disease-free men selected from the Health Professionals' Follow-up Study to provide information on a range of drinking patterns. Study participants were 48 to 82 years of age who provided a blood sample and detailed information on diet, life-style and alcohol consumption patterns in 1994. Among the study participants, 267 men provided a fasting blood sample and contributed to the analyses of insulin and c-peptide. RESULTS: Biologic markers were not strongly related to average alcohol consumption. Compared to abstainers, differences in insulin concentrations-all statistically non-significant-were 0.06, 1.25, 1.02, and 0.12 micro U/mL for consumers of <1, 1-1.9, 2-2.9, 3+ drinks per day, respectively. The frequency of alcohol consumption was inversely related to fasting c-peptide and insulin concentrations after controlling for average alcohol consumption and other potential confounding variables. Compared to men who reported consuming alcohol one to three days per week, c-peptide concentrations were 0.08 ng/mL and 0.29 ng/mL lower (p-trend = 0.04) in men who reported consuming alcohol on four to five days per week and six to seven days per week, respectively. Men who consumed alcohol on most days also had lower fasting insulin levels than more irregular drinkers (p-trend = 0.05). CONCLUSIONS: Our results suggest that frequent alcohol consumption is inversely related to fasting c-peptide and insulin concentrations.

Adult↗
PubMed2003

Body iron stores and their determinants in healthy postmenopausal US women.

BACKGROUND: Data on the determinants of body iron stores in middle-aged women are sparse. OBJECTIVE: We prospectively evaluated nondietary and dietary determinants of iron stores. DESIGN: Using blood samples collected in 1989-1990, we measured plasma ferritin concentrations in 620 healthy postmenopausal women aged 44-69 y who participated in the Nurses' Health Study. Food-frequency questionnaires completed in 1980, 1984, and 1986 were used to calculate average dietary intakes. Generalized linear regression and multiple logistic regression models were used to assess the association between plasma ferritin and its determinants. RESULTS: Among these postmenopausal women, the median plasma ferritin concentration was 73.8 ng/mL (interquartile range: 41.6-125.8 ng/mL), 2.7% were iron depleted (ferritin concentration < 12 ng/mL), and 9.8% had an elevated ferritin concentration (> 200 ng/mL). Age, time since menopause, time since the last postmenopausal hormone (PMH) use, body mass index, iron supplement use, and alcohol and heme-iron intakes were positively associated with ferritin concentrations, whereas PMH use, physical activity, aspirin use, and gastrointestinal ulcer were inversely related. The association between heme-iron intake and ferritin was most apparent among the women who consumed > 30 g alcohol/d. CONCLUSIONS: Our prospective data confirm that in postmenopausal women, intakes of heme iron, supplemental iron, and alcohol are dietary determinants of plasma ferritin, and age, PMH use, body mass index, physical activity, aspirin use, and gastrointestinal ulcer are nondietary determinants.

Adult↗
PubMed2003

Standardization of immunoassays for measurement of high-sensitivity C-reactive protein. Phase I: evaluation of secondary reference materials.

BACKGROUND: Inflammation contributes to the development and progression of atherosclerosis, and C-reactive protein (CRP) can be used as a marker to assess risk for cardiovascular diseases. As variability among existing high-sensitivity CRP (hsCRP) assays can lead to misclassification of patients and hamper implementation of population-based medical decision points, standardization of hsCRP assays is needed. METHODS: We evaluated five proposed secondary reference materials, including two diluted preparations of Certified Reference Material 470 (CRM470), two preparations of a serum-based material with recombinant CRP added, and one serum-based material with isolated CRP added. Twenty-one manufacturers participated in the comparison with 28 different assays. We examined imprecision, linearity, and parallelism with these materials and with fresh serum. RESULTS: All materials had similar imprecision; CVs for the undiluted materials were 2.1-3.7%. None of the materials was linear across all assays. Each had between one and three cases of nonlinearity, with one preparation of CRM470 having the fewest cases of nonlinearity. Although none of the materials was parallel across all assays, the differences in slope from fresh serum were similar across all assays. CONCLUSIONS: All materials performed similarly with regard to imprecision, linearity, and parallelism. As one preparation of CRM470 had slightly better characteristics than the other materials and because CRM470 had been certified previously as a reference material for the acute-phase reactant range, it will be used in the next phase to standardize hsCRP assays.

C-Reactive Protein↗
PubMed2003

Preanalytic and analytic sources of variations in C-reactive protein measurement: implications for cardiovascular disease risk assessment.

BACKGROUND: C-reactive protein (CRP) is a widely recognized indicator of inflammation and is known to play an important role in atherogenesis. Recent prospective studies have demonstrated that increased CRP concentrations within the reference interval are a strong predictor of myocardial infarction, stroke, sudden cardiac death, and peripheral vascular disease in apparently healthy adults. On the basis of available evidence, the American Heart Association and the CDC have issued guidelines for the utility of CRP in the primary prevention of coronary heart disease and in patients with stable coronary disease or acute coronary syndromes. Nevertheless, there remains considerable work to optimize the utility of this marker for risk assessment. ISSUES: Most traditional CRP tests designed to monitor acute and chronic inflammation have inadequate sensitivity for risk stratification of coronary disease. Thus, manufacturers have had to develop tests with higher sensitivity. Because an individual's CRP concentration will be interpreted according to fixed cut-points, issues related to the preanalytic and analytic components of CRP measurement must be considered and standardized where possible to avoid potential misclassification of cardiovascular risk. CONCLUSIONS: Efforts to define performance criteria for high-sensitivity CRP applications coupled with growing awareness of the physiologic aspects of CRP most likely will lead to refinements in standardization, improved performance in quality-assessment schemes, and enhanced risk prediction.

Animals↗
PubMed2003

C-reactive protein concentration distribution among US children and young adults: findings from the National Health and Nutrition Examination Survey, 1999-2000.

BACKGROUND: The distribution of C-reactive protein (CRP) concentrations among children and young adults in the US is not known at present. METHODS: We used data from 3348 US children and young adults 3-19 years of age who participated in the National Health and Nutrition Examination Survey, 1999-2000, to describe the distribution of CRP concentrations, based on results obtained with a high-sensitivity latex-enhanced turbidimetric assay. RESULTS: The range of CRP concentrations was 0.1-90.8 mg/L (mean, 1.6 mg/L; geometric mean, 0.5 mg/L; median, 0.4 mg/L). CRP concentrations increased with age. Females 16-19 years of age had higher concentrations than males in this age range (P = 0.003). Mexican Americans had the highest CRP concentrations among the three major race or ethnic groups (P <0.001). CONCLUSIONS: For the first time, these data describe the CRP concentration distribution among US children and young adults, based on results obtained with a high-sensitivity assay.

Adolescent↗
PubMed2003

Serum cardiac troponin and subclinical cardiac status in pediatric chronic renal failure.

BACKGROUND: Patients with uremia often have elevated serum cardiac troponin T (cTnT) even without clinical heart damage. Pediatric patients are ideal for studies of the relationship between uremia and heart disease because they are unlikely to have cardiac risk factors other than uremia. OBJECTIVE: To determine the relationship between uremia and cTnT levels. DESIGN: Echocardiograms and blood chemistry results were obtained from 50 pediatric patients with chronic renal failure and without clinical heart disease. Levels of cTnT were tested for correlation with cardiac dysfunction. In multivariate analysis, biochemical aspects of renal disease and its treatment were tested for correlation with cardiac dysfunction. RESULTS: Forty-nine patients had cardiovascular abnormalities, including increased left ventricular function and mass, elevated heart rate and blood pressure, and reduced LV afterload. LV contractility was inversely correlated with cTnT level (r = -0.36). Higher cTnT also correlated with higher serum creatine kinase-MB mass, lower serum parathyroid hormone, higher blood urea nitrogen and bicarbonate levels, and the use of diuretics, but not with higher cardiac troponin I. Left ventricular contractility was inversely related to serum creatinine, phosphorus, and the use of beta-blockers. CONCLUSIONS: Elevated cTnT levels are not artifactual, but are genuine indicators of cardiomyocyte damage. Cardiac damage, indicated by either elevated cTnT or low LV contractility, is related to uremia, deranged calcium and phosphorus metabolism, and bicarbonate levels. Serum cTnT and LV contractility identify subclinical cardiac damage that could be treated to hopefully reduce cardiovascular morbidity and mortality in this high-risk population.

Adolescent↗
PubMed2003

A cross-sectional study of alcohol consumption patterns and biologic markers of glycemic control among 459 women.

OBJECTIVE: Little research has explored associations of drinking patterns with glycemic control, especially among women. Our objective was to determine the relationship of patterns of alcohol consumption-including average daily consumption, weekly frequency of consumption, drinking with meals, and beverage type-with biologic markers of insulin resistance in young women. RESEARCH DESIGN AND METHODS: This study was cross-sectional in design. The subjects consisted of a stratified random subpopulation of 459 U.S. normal-weight and overweight female nurses, 33-50 years of age, drawn from the Nurses' Health Study II and sampled for distinct drinking patterns. Women provided blood samples and detailed information on dietary and lifestyle factors between 1995 and 1999. The main outcome measures were fasting insulin, C-peptide, and HbA(1c). RESULTS: Adjusting for age, smoking, physical activity, television watching, BMI, and several dietary factors, average alcohol intake was inversely associated with HbA(1c) (units in percentage of HbA(1c)): 0 g/day (reference = 5.36%), 0.1 to <5.0 g/day (-0.04%), 5.0 to <15.0 g/day (-0.09%), 15.0 to <25.0 g/day (-0.10%), and > or =25.0 g/day (-0.17%) (P value, test for trend <0.001). We found an inverse association of alcohol intake and insulin, but only for women with a BMI > or =25 kg/m(2). Specifically, insulin levels were lowest for episodic drinkers consuming > or =2 drinks per day on 0-3 days per week. Consumption with meals and type of alcoholic beverage did not further influence these results. CONCLUSIONS: Moderate alcohol consumption of 1-2 drinks per day on a few to several days of the week may have a beneficial glycemic effect, particularly among overweight women.

Adult↗
PubMed2003

Association of markers of insulin and glucose control with subsequent colorectal cancer risk.

We evaluated the association of plasma insulin and other markers of insulin and glucose control with subsequent colorectal cancer. Incident colon (n = 132) and rectal (n = 41) cancer cases and matched controls (n = 346) were identified between baseline in 1989 and 2000 among participants in a community-based cohort in Washington County, Maryland. Circulating markers of insulin and glucose control were measured in baseline blood samples. Body mass index (BMI) and use of medications to treat diabetes mellitus were self-reported at baseline. Conditional logistic regression was used to estimate matched odds ratios (ORs). Compared with the lowest fourth, participants with insulin concentrations in the highest fourth were not at an increased risk of colorectal cancer [OR, 0.78; 95% confidence interval (CI), 0.45-1.35; P(trend) = 0.24]. Similarly, no associations were observed for the ratio of total cholesterol:HDL-cholesterol, triglycerides, and insulin-like growth factor binding protein 1. However, those in the highest fourth of glycosylated hemoglobin (HbA(1c)) level had a slightly increased risk of colorectal cancer (OR, 1.57; 95% CI, 0.94-2.60; P(trend) = 0.02). The OR of colorectal cancer was 1.70 (95% CI, 1.01-2.86; P(trend) = 0.08) comparing BMI >/=30 kg/m(2) to <25 kg/m(2). The OR of colorectal cancer was 2.43 (95% CI, 1.10-5.38) for the use of medications to treat diabetes. The associations of higher HbA(1c), higher BMI, and the use of medications to treat diabetes, with colorectal cancer lend support to the hypothesis that perturbations in insulin and glucose control may influence colorectal carcinogenesis. It is possible that HbA(1c), BMI, and the use of medications to treat diabetes, as a surrogate for protracted or severe type 2 diabetes mellitus, may have been better time-averaged indicators of hyperinsulinemia and hyperglycemia than the plasma markers that were measured once prediagnostically in a nonfasting population.

Adult↗