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Biomedical subjects

Nader Rifai

Publications and source records attributed to Nader Rifai.

At least 91 records · Page 5Linked to original sources
PubMed2004

Dietary intake of trans fatty acids and systemic inflammation in women.

BACKGROUND: trans Fatty acid (TFA) intake predicts risks of coronary artery disease and diabetes. Systemic inflammation may be involved in the pathogenesis of such conditions; however, relations between TFA intake and systemic inflammation are not well established. OBJECTIVE: We investigated the relations between TFA intake and inflammatory markers. DESIGN: In 823 generally healthy women in the Nurses' Health Study I and II, concentrations of soluble tumor necrosis factor alpha receptors 1 and 2 (sTNF-R1, sTNF-R2), interleukin 6 (IL-6), and C-reactive protein (CRP) were measured. Usual dietary intakes assessed from 2 semiquantitative food-frequency questionnaires were averaged for each subject. RESULTS: In age-adjusted analyses, TFA intake was positively associated with sTNF-R1 and sTNF-R2 (P for trend < 0.001 for each): sTNF-R1 and sTNF-R2 concentrations were 10% (+108 pg/mL; 95% CI: 50, 167 pg/mL) and 12% (+258 pg/mL; 138, 377 pg/mL) higher, respectively, in the highest intake quintile than in the lowest. These associations were not appreciably altered by adjustment for body mass index, smoking, physical activity, aspirin and nonsteroidal antiinflammatory drug use, alcohol consumption, and intakes of saturated fat, protein, n-6 and n-3 fatty acids, fiber, and total energy. Adjustment for serum lipid concentrations partly attenuated these associations, which suggests that they may be partly mediated by effects of TFAs on serum lipids. TFA intake was not associated with IL-6 or CRP concentrations overall but was positively associated with IL-6 and CRP in women with higher body mass index (P for interaction = 0.03 for each). CONCLUSIONS: TFA intake is positively associated with markers of systemic inflammation in women. Further investigation of the influences of TFAs on inflammation and of implications for coronary disease, diabetes, and other conditions is warranted.

Adult↗
PubMed2004

Major dietary patterns are related to plasma concentrations of markers of inflammation and endothelial dysfunction.

BACKGROUND: Endothelial dysfunction is one of the mechanisms linking diet and the risk of cardiovascular disease. OBJECTIVE: We evaluated the hypothesis that dietary patterns (summary measures of food consumption) are directly associated with markers of inflammation and endothelial dysfunction, particularly C-reactive protein (CRP), interleukin 6, E-selectin, soluble intercellular adhesion molecule 1 (sICAM-1), and soluble vascular cell adhesion molecule 1 (sVCAM-1). DESIGN: We conducted a cross-sectional study of 732 women from the Nurses' Health Study I cohort who were 43-69 y of age and free of cardiovascular disease, cancer, and diabetes mellitus at the time of blood drawing in 1990. Dietary intake was documented by using a validated food-frequency questionnaire in 1986 and 1990. Dietary patterns were generated by using factor analysis. RESULTS: A prudent pattern was characterized by higher intakes of fruit, vegetables, legumes, fish, poultry, and whole grains, and a Western pattern was characterized by higher intakes of red and processed meats, sweets, desserts, French fries, and refined grains. The prudent pattern was inversely associated with plasma concentrations of CRP (P = 0.02) and E-selectin (P = 0.001) after adjustment for age, body mass index (BMI), physical activity, smoking status, and alcohol consumption. The Western pattern showed a positive relation with CRP (P < 0.001), interleukin 6 (P = 0.006), E-selectin (P < 0.001), sICAM-1 (P < 0.001), and sVCAM-1 (P = 0.008) after adjustment for all confounders except BMI; with further adjustment for BMI, the coefficients remained significant for CRP (P = 0.02), E-selectin (P < 0.001), sICAM-1 (P = 0.002), and sVCAM-1 (P = 0.02). CONCLUSION: Because endothelial dysfunction is an early step in the development of atherosclerosis, this study suggests a mechanism for the role of dietary patterns in the pathogenesis of cardiovascular disease.

Adult↗
PubMed2004

Fructose, glycemic load, and quantity and quality of carbohydrate in relation to plasma C-peptide concentrations in US women.

BACKGROUND: Circulating C-peptide concentrations are associated with insulin resistance and the development of type 2 diabetes. However, associations between fructose and the quantity and quality of total carbohydrate intake in relation to C-peptide concentrations have not been adequately examined. OBJECTIVE: We assessed the association of dietary fructose, glycemic load, and carbohydrate intake with fasting C-peptide concentrations. DESIGN: Plasma C-peptide concentrations were measured in a cross-sectional setting in 1999 healthy women from the Nurses' Health Study I and II. Dietary fructose, glycemic load, and carbohydrate intake were assessed with the use of semiquantitative food-frequency questionnaires. RESULTS: After multivariate adjustment, subjects in the highest quintile of energy-adjusted fructose intake had 13.9% higher C-peptide concentrations (P for trend = 0.01) than did subjects in the lowest quintile. Similarly, in the multivariate model, subjects in the highest quintile of glycemic load had 14.1% (P for trend = 0.09) and 16.1% (P for trend = 0.04) higher C-peptide concentrations than did subjects in the lowest quintile after further adjustment for total fat or carbohydrate intake, respectively. In contrast, subjects with high intakes of cereal fiber had 15.6% lower (P for trend = 0.03) C-peptide concentrations after control for other covariates. CONCLUSIONS: Our results suggest that high intakes of fructose and high glycemic foods are associated with higher C-peptide concentrations, whereas consumption of carbohydrates high in fiber, such as whole-grain foods, is associated with lower C-peptide concentrations. Furthermore, our study suggests that these nutrients play divergent roles in the development of insulin resistance and type 2 diabetes.

Adult↗
PubMed2004

Consumption of (n-3) fatty acids is related to plasma biomarkers of inflammation and endothelial activation in women.

We evaluated the hypothesis that intake of (n-3) fatty acids is inversely associated with biomarkers of inflammation and endothelial activation. We conducted a cross-sectional study of 727 women from the Nurses' Health Study I cohort, aged 43-69 y, apparently healthy at time of a blood draw in 1990. Dietary intake was assessed by a validated FFQ in 1986 and 1990. C-reactive protein (CRP) levels were 29% lower among those in the highest quintile of total (n-3) fatty acids, compared with the lowest quintile; interleukin-6 (IL-6) levels were 23% lower, E-selectin levels 10% lower, soluble intracellular adhesion molecule (sICAM-1) levels 7% lower, and soluble vascular adhesion molecule (sVCAM-1) levels 8% lower. The intake of alpha-linolenic acid was inversely related to plasma concentrations of CRP (beta = -0.55, P = 0.02), Il-6 (beta = -0.36, P = 0.01), and E-selectin (beta = -0.24, P = 0.008) after controlling for age, BMI, physical activity, smoking status, alcohol consumption, and intake of linoleic acid (n-6) and saturated fat. Long-chain (n-3) fatty acids (eicosapentaenoic and docosahexaenoic) were inversely related to sICAM-1 (beta = -0.11, P = 0.03) and sVCAM-1 (beta = -0.17, P = 0.003). Total (n-3) fatty acids had an inverse relation with CRP (beta = -0.44, P = 0.007), IL-6 (beta = -0.26, P = 0.009), E-selectin (beta = -0.17, P = 0.004), sICAM-1 (beta = -0.07, P = 0.02), and sVCAM-1 (beta = -0.10, P = 0.004). These associations were not modified by intake of vitamin E, dietary fiber, trans fatty acids, or by the use of postmenopausal hormone therapy. In conclusion, this study suggests that dietary (n-3) fatty acids are associated with levels of these biomarkers reflecting lower levels of inflammation and endothelial activation, which might explain in part the effect of these fatty acids in preventing cardiovascular disease.

Adult↗
PubMed2004

Inflammatory markers and risk of developing type 2 diabetes in women.

We conducted a prospective, nested, case-control study of inflammatory markers as predictors of type 2 diabetes among 32,826 women who provided blood samples in 1989 through 1990 in the Nurses' Health Study. Among women free of diabetes, cardiovascular disease, or cancer at baseline, 737 had developed diabetes by 2000. Control women (n = 785) were selected matched on age, fasting status, race, and BMI for cases in the top BMI decile. Baseline levels of tumor necrosis factor (TNF)-alpha receptor 2, interleukin (IL)-6, and C-reactive protein (CRP) were significantly higher among case than control subjects (all P </= 0.001). After adjusting for BMI and other lifestyle factors, all three biomarkers significantly predicted diabetes risk; the odds ratios (ORs) comparing extreme quintiles were 1.64 (95% CI 1.10-2.45) for TNF-alphaR2, 1.91 (1.27-2.86) for IL-6, and 4.36 (2.80-6.80) for CRP (P for trend <0.001 for all biomarkers). In a multivariate model simultaneously including the three biomarkers, only CRP levels were significantly associated with risk of diabetes (OR comparing extreme quintiles of CRP = 3.99, P for trend <0.001). These data support the role of inflammation in the pathogenesis of type 2 diabetes. Elevated CRP levels are a strong independent predictor of type 2 diabetes and may mediate associations of TNF-alphaR2 and IL-6 with type 2 diabetes.

Adult↗
PubMed2004

C-reactive protein and incident cardiovascular events among men with diabetes.

OBJECTIVE: Several large prospective studies have shown that baseline levels of C-reactive protein (CRP) are an independent predictor of cardiovascular events among apparently healthy individuals. However, prospective data on whether CRP predicts cardiovascular events in diabetic patients are limited so far. RESEARCH DESIGN AND METHODS: To investigate the association between plasma CRP levels and incidence of cardiovascular events among men with type 2 diabetes, we followed prospectively a cohort of 746 American men aged 46-81 years who were free of cardiovascular diseases at the time of blood collection in 1993-1994. RESULTS: During an average of 5 years of follow-up (3,986 person-years), we identified 103 incident cardiovascular events (18 myocardial infarction, 70 coronary artery bypass grafting or angioplasty, and 15 stroke), confirmed by medical records. After adjustment for age, BMI, smoking, alcohol consumption, physical activity, family history of coronary heart disease, history of high blood pressure, history of high serum cholesterol, aspirin use, and fasting status as well as for fibrinogen, creatinine, HbA(1c), and non-HDL cholesterol levels, CRP remained significantly associated with an increased risk of cardiovascular events. The relative risks for quartiles were 1.00, 1.51, 2.52, and 2.62 (95% CI: 1.29-5.32; P for trend: 0.011). We observed no effect modifications by plasma levels of LDL cholesterol, HDL cholesterol, non-HDL cholesterol, apolipoprotein B, HbA(1c), and fibrinogen or by BMI. CONCLUSIONS: High plasma levels of CRP were associated with an increased risk of incident cardiovascular events among diabetic men, independent of currently established lifestyle risk factors, blood lipids, and glycemic control.

Aged↗
PubMed2004

Relationship between adiponectin and glycemic control, blood lipids, and inflammatory markers in men with type 2 diabetes.

OBJECTIVE: Adiponectin, synthesized in the adipose tissue, appears to play an important role in hyperglycemia and dyslipidemia, as well as in inflammatory mechanisms, which lead to a markedly increased atherosclerotic risk in diabetic subjects. However, previous studies did not evaluate the complex relationships between adiponectin and the array of metabolic abnormalities commonly observed in diabetes. RESEARCH DESIGN AND METHODS: To examine the associations between plasma levels of adiponectin and HbA(1c), blood lipids, and inflammatory markers, we obtained blood samples from 741 participants in the Health Professionals Follow-up Study with a diagnosis of type 2 diabetes. RESULTS: Plasma adiponectin levels were positively correlated with HDL cholesterol and negatively correlated with triglycerides, apolipoprotein B-100 (apoB(100)), C-reactive protein (CRP), and fibrinogen. These associations were not appreciably altered after controlling for lifestyle exposures, medical conditions, and obesity-associated variables. A 10-microg/ml higher level of plasma adiponectin was associated with lower HbA(1c) (-0.21% points, P = 0.001), triglycerides (-0.39 mmol/l, P < 0.001), apoB(100) (-0.04 g/l, P < 0.001), CRP (-0.51 mg/l, P = 0.003), and fibrinogen (-0.53 micromol/l, P < 0.001) and higher HDL cholesterol (0.13 mmol/l, P < 0.001). Associations between adiponectin and inflammatory markers were furthermore independent of HbA(1c) and HDL cholesterol, suggesting that the anti-inflammatory properties of adiponectin are not mediated by potential effects on glycemic control and blood lipids. Our results were consistent among obese and nonobese men. CONCLUSIONS: Our study supports the hypothesis that increased adiponectin levels might be associated with better glycemic control, better lipid profile, and reduced inflammation in diabetic subjects. Measures that increase adiponectin levels might be valuable targets for decreasing the atherosclerotic risk present in diabetes.

Adiponectin↗
PubMed2004

Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes.

OBJECTIVE: To evaluate the role of non-HDL cholesterol and apolipoprotein (apo)B, markers of all potentially atherogenic lipoproteins, as predictors of cardiovascular disease (CVD) in comparison with LDL cholesterol in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: We prospectively followed 746 diabetic men in the Health Professionals' Follow-up Study who were aged 46-81 years and free of CVD or cancer at the time of blood draw in 1993-1994. During 6 years of follow-up, we ascertained 103 incident CVD cases. RESULTS: We used Cox proportional hazard modeling to estimate the relative risk (RR) of CVD. After adjustment for age, BMI, and other lifestyle risk factors, the multivariate RR of CVD (the highest versus the lowest quartile) was 2.34 (95% CI 1.26-4.32) for non-HDL cholesterol, 2.31 (1.23-4.35) for apoB, and 1.74 (0.99-3.06) for LDL cholesterol. Comparisons of nested models indicate that non-HDL cholesterol, but not apoB, adds significantly to the prediction of CVD risk beyond LDL cholesterol. The area under the receiver operating characteristic curve was 0.685, 0.691, 0.695, and 0.722 for the CVD risk-prediction model with LDL cholesterol, apoB, non-HDL cholesterol, and total cholesterol-to-HDL cholesterol ratio (or the non-HDL-to-HDL cholesterol ratio), respectively. CONCLUSIONS: Non-HDL cholesterol and apoB are more potent predictors of CVD incidence among diabetic men than LDL cholesterol. Statistically, the ratio of total to HDL cholesterol is the best predictor of CVD in this cohort of diabetic men.

Aged↗
PubMed2004

Plasma adrenal androgens and risk of breast cancer in premenopausal women.

OBJECTIVES: Plasma DHEA and its sulfate (DHEA-S) are positively associated with breast cancer risk in postmenopausal women; but the relationships have not been studied in detail in premenopausal women. We prospectively evaluated relationships between plasma levels of DHEA and DHEA-S in blood samples provided by a group of primarily premenopausal women and subsequent breast cancer, by use of case-control sampling from the Nurses' Health Study cohort. METHOD: Blood samples were collected from 1989 to 1990. Among women who were not postmenopausal at blood collection, 302 were diagnosed with breast cancer between blood collection and June 1998. Two controls were selected per case and matched with respect to age, menopausal status, month and time of day of blood collection, and fasting status at blood collection. Statistical analyses using conditional logistic regression were done to adjust for potential confounders. RESULTS: At time of blood collection, the median age was 49 (10th to 90th percentiles 45 to 53). In multivariable analyses, the highest quartile of DHEA was associated with an odds ratio of breast cancer of 0.92 (95% confidence interval, 0.59-1.43) relative to the lowest quartile (P value for log-linear trend 0.11). A similar analysis revealed an odds ratio of 1.08 (0.69-1.69) for DHEA-S (P value for log-linear trend 0.83). No statistically significant interactions were noted according to certainty of menopausal status, age, or past oral contraceptive use. DISCUSSION: Our analysis did not reveal a relationship between DHEA or DHEA-S and subsequent breast cancer in middle-aged premenopausal women. In the future, this relationship should be studied in younger women.

Androgens↗
PubMed2004

High-sensitivity C-reactive protein: clinical importance.

High-sensitivity C-reactive protein (hsCRP) is a marker of inflammation that predicts incident myocardial infarction, stroke, peripheral arterial disease, and sudden cardiac death among healthy individuals with no history of cardiovascular disease, and recurrent events and death in patients with acute or stable coronary syndromes. hsCRP confers additional prognostic value at all levels of cholesterol, Framingham coronary risk score, severity of the metabolic syndrome, and blood pressure, and in those with and without subclinical atherosclerosis. hsCRP levels of less than 1, 1 to 3, and greater than 3 mg/L are associated with lower, moderate, and higher cardiovascular risks, respectively. This article summarizes epidemiologic data on the relation between CRP and atherothrombotic disease and provides clinical guidelines for hsCRP screening in cardiovascular risk assessment.

C-Reactive Protein↗
PubMed2004

Stability of measurements of biomarkers of oxidative stress in blood over 36 hours.

Oxidative stress is hypothesized to play an important role in a variety of chronic diseases, but the short-term and long-term stability of measurements of biomarkers related to oxidative stress remains unclear. The objective of this study was to evaluate the stability of measurements of malondialdehyde (MDA), F2-isoprostanes, and fluorescent oxidation products in blood stored on ice within 36 hours until processing. Whole blood samples from six healthy women were processed at 0, 24, and 36 hours after being stored on ice. MDA was measured by the thiobarbituric acid-reactive substances assay with high-pressure liquid chromatography. F2-isoprostanes were measured by gas chromatography/mass spectrometry. The fluorescent oxidation products were measured by spectrofluorometry. Measurements of fluorescent oxidation products were very stable up to 36 hours. Intraclass correlation coefficients (ICC) were >0.95 for each time interval (0 to 24 and 0 to 36 hours). Measurements of MDA were the least stable. The median increased significantly from 0 to 24 hours and from 0 to 36 hours. The ICC for MDA for each time interval (0 to 24 and 0 to 36 hours) was <0.1. Finally, the median of F2-isoprostane measurements at each time point also increased significantly. ICCs were 0.45 for 0 to 24 hours and 0.09 for 0 to 36 hours. We conclude that measurements of fluorescent oxidation products in blood remain stable for up to 36 hours and may be used in large prospective epidemiologic studies of chronic diseases.

Adult↗
PubMed2003

C-reactive protein and the risk of developing hypertension.

CONTEXT: Although it has been hypothesized that hypertension is in part an inflammatory disorder, clinical data linking inflammation with incident hypertension are scarce. OBJECTIVE: To examine whether C-reactive protein levels, a marker of systemic inflammation, are associated with incident hypertension. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study that began in 1992 of 20 525 female US health professionals aged 45 years or older who provided baseline blood samples with initially normal levels of blood pressure (BP) (systolic BP <140 mm Hg and diastolic BP <90 mm Hg, and no history of hypertension or antihypertensive medications) and then followed up for a median of 7.8 years for the development of incident hypertension. Plasma C-reactive protein levels were measured and baseline coronary risk factors were collected. MAIN OUTCOME MEASURE: Incident hypertension, defined as either a new physician diagnosis, the initiation of antihypertensive treatment, or self-reported systolic BP of at least 140 mm Hg or a diastolic BP of at least 90 mm Hg. RESULTS: During follow-up, 5365 women developed incident hypertension. In crude models, the relative risks (RRs) and 95% confidence intervals (CIs) of developing hypertension from the lowest (referent) to the highest levels of baseline C-reactive protein were 1.00, 1.25 (95% CI, 1.14-1.40), 1.51 (95% CI, 1.35-1.68), 1.90 (95% CI, 1.72-2.11), and 2.50 (95% CI, 2.27-2.75) (linear trend P<.001). In fully adjusted models for coronary risk factors, the RRs and 95% CIs were 1.00, 1.07 (95% CI, 0.95-1.20), 1.17 (95% CI, 1.04-1.31), 1.30 (95% CI, 1.17-1.45), and 1.52 (95% CI, 1.36-1.69) (linear trend P<.001). C-reactive protein was significantly associated with an increased risk of developing hypertension in all prespecified subgroups evaluated, including those with very low levels of baseline BP, as well as those with no traditional coronary risk factors. Similar results were found when treating C-reactive protein as a continuous variable and controlling for baseline BP. CONCLUSION: C-reactive protein levels are associated with future development of hypertension, which suggests that hypertension is in part an inflammatory disorder.

Biomarkers↗
PubMed2003

Blood pressure, C-reactive protein, and risk of future cardiovascular events.

BACKGROUND: Accumulating data suggest a link between blood pressure and vascular inflammation. METHODS AND RESULTS: We examined the relationship between blood pressure, C-reactive protein (CRP), and incident first cardiovascular events among 15 215 women followed prospectively over a median of 8.1 years. In cross-sectional analyses at baseline, median levels of CRP for women with blood pressure <120/75, 120 to 129/75 to 84, 130 to 139/85 to 89, 140 to 159/90 to 94, and > or =160/95 mm Hg were 0.96, 1.42, 2.20, 2.82, and 3.34 mg/L, respectively (P for trend <0.0001). Increasing categories of blood pressure were significant predictors of CRP levels at baseline. In prospective analyses, both elevated CRP levels (> or =3 mg/L) and increasing categories of blood pressure were independent determinants of future cardiovascular events, and CRP had incremental prognostic value at all levels of blood pressure. The adjusted hazard ratio for women with blood pressure > or =160/95 mm Hg and CRP levels > or =3 mg/L was 8.31 (95% CI, 4.44 to 15.55, P<0.0001) compared with those with blood pressure <120/75 and CRP levels <3 mg/L. After participants had been divided into 4 groups on the basis of CRP levels (<3 or > or =3 mg/L) and blood pressure levels (<130/85 or > or =130/85), the risk factor-adjusted hazard ratios were as follows: low CRP/low blood pressure, 1.0; high CRP/low blood pressure, 1.87 (P=0.002); low CRP/high blood pressure, 2.54 (P<0.0001); and high CRP/high blood pressure, 3.27 (P<0.0001). CONCLUSIONS: CRP and blood pressure are independent determinants of cardiovascular risk, and their predictive value is additive.

Blood Pressure↗
PubMed2003

High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study.

BACKGROUND: Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. METHODS AND RESULTS: We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 or > or =3.2 mmol/L (125 mg/dL), age > or =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. CONCLUSIONS: High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.

Acute Disease↗
PubMed2003

Antioxidant vitamins C and E improve endothelial function in children with hyperlipidemia: Endothelial Assessment of Risk from Lipids in Youth (EARLY) Trial.

BACKGROUND: Hyperlipidemia is associated with endothelial dysfunction, an early event in atherosclerosis and predictor of risk for future coronary artery disease. Epidemiological studies suggest that increased dietary intake of antioxidants reduces the risk of coronary artery disease. The purpose of this study was to determine whether antioxidant vitamin therapy improves endothelial function and affects surrogate biomarkers for oxidative stress and inflammation in hyperlipidemic children. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled trial, the effects of antioxidant vitamins C (500 mg/d) and E (400 IU/d) for 6 weeks and the National Cholesterol Education Program Step II (NCEP-II) diet for 6 months on endothelium-dependent flow-mediated dilation (FMD) of the brachial artery were examined in 15 children with familial hypercholesterolemia (FH) or the phenotype of familial combined hyperlipidemia (FCH). Antioxidant vitamin therapy improved FMD of the brachial artery compared with baseline (P<0.001) without an effect on biomarkers for oxidative stress (autoantibodies to epitopes of oxidized LDL, F2-isoprostanes, 8-hydroxy-2'-deoxyguanosine), inflammation (C-reactive protein), or levels of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide. CONCLUSIONS: Antioxidant therapy with vitamins C and E restores endothelial function in hyperlipidemic children. Early detection and treatment of endothelial dysfunction in high-risk children may retard the progression of atherosclerosis.

Adolescent↗
PubMed2003

Relation of levels of hemostatic factors and inflammatory markers to the ankle brachial index.

Associations between hemostatic and inflammatory markers relative to the ankle brachial index (ABI), an indicator of the presence and severity of peripheral arterial disease (PAD), are not fully understood. We studied relations among selected hemostatic factors, inflammatory markers, and the ankle brachial index (ABI) in patients with and without peripheral arterial disease (PAD). Participants were 370 men and women with ABI <0.90 and 231 patients with ABI 0.90 to 1.50 identified from noninvasive vascular laboratories and general medicine practice. Blood factors were D-dimer, prothrombin 1.2, tissue plasminogen activator (t-PA) antigen, plasminogen activator inhibitor-1 (PAI-1), and inflammatory markers (high-sensitivity C-reactive protein [CRP], fibrinogen, and serum amyloid A [SAA]). Among patients without a history of cardiac or cerebrovascular disease, the ABI was significantly inversely associated with log D-dimer (p <0.001), log prothrombin 1.2 (p = 0.001), log CRP (p <0.001), and log fibrinogen (p = 0.005) in unadjusted analyses. In multivariable regression analyses adjusting for all blood factors as well as potential confounders, D-dimer was associated independently with ABI in participants with a history of cardiac or cerebrovascular disease (p = 0.003) and in participants without a history of cardiac or cerebrovascular disease (p = 0.017). In these analyses, CRP was associated independently with ABI among participants with a history of cardiac or cerebrovascular disease (p = 0.026). CRP was not associated independently with ABI in participants without a history of cardiac or cerebrovascular disease. We conclude that D-dimer levels may be more sensitive than other blood markers for measuring the extent of atherosclerosis in lower extremity arteries.

Aged↗