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Nader Rifai

Publications and source records attributed to Nader Rifai.

At least 127 records · Page 7Linked to original sources
PubMed2002

Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.

BACKGROUND: Both C-reactive protein and low-density lipoprotein (LDL) cholesterol levels are elevated in persons at risk for cardiovascular events. However, population-based data directly comparing these two biologic markers are not available. METHODS: C-reactive protein and LDL cholesterol were measured at base line in 27,939 apparently healthy American women, who were then followed for a mean of eight years for the occurrence of myocardial infarction, ischemic stroke, coronary revascularization, or death from cardiovascular causes. We assessed the value of these two measurements in predicting the risk of cardiovascular events in the study population. RESULTS: Although C-reactive protein and LDL cholesterol were minimally correlated (r=0.08), base-line levels of each had a strong linear relation with the incidence of cardiovascular events. After adjustment for age, smoking status, the presence or absence of diabetes mellitus, categorical levels of blood pressure, and use or nonuse of hormone-replacement therapy, the relative risks of first cardiovascular events according to increasing quintiles of C-reactive protein, as compared with the women in the lowest quintile, were 1.4, 1.6, 2.0, and 2.3 (P<0.001), whereas the corresponding relative risks in increasing quintiles of LDL cholesterol, as compared with the lowest, were 0.9, 1.1, 1.3, and 1.5 (P<0.001). Similar effects were observed in separate analyses of each component of the composite end point and among users and nonusers of hormone-replacement therapy. Overall, 77 percent of all events occurred among women with LDL cholesterol levels below 160 mg per deciliter (4.14 mmol per liter), and 46 percent occurred among those with LDL cholesterol levels below 130 mg per deciliter (3.36 mmol per liter). By contrast, because C-reactive protein and LDL cholesterol measurements tended to identify different high-risk groups, screening for both biologic markers provided better prognostic information than screening for either alone. Independent effects were also observed for C-reactive protein in analyses adjusted for all components of the Framingham risk score. CONCLUSIONS: These data suggest that the C-reactive protein level is a stronger predictor of cardiovascular events than the LDL cholesterol level and that it adds prognostic information to that conveyed by the Framingham risk score.

Aged↗
PubMed2002

Low-density lipoprotein particle concentration and size as determined by nuclear magnetic resonance spectroscopy as predictors of cardiovascular disease in women.

BACKGROUND: Nuclear magnetic resonance (NMR) offers an alternative, spectroscopic means of quantifying LDL and of measuring LDL particle size. METHODS AND RESULTS: We conducted a prospective nested case-control study among healthy middle-aged women to assess LDL particle size (NMR) and concentration (NMR) as risk factors for future myocardial infarction, stroke, or death of coronary heart disease. Median baseline levels of LDL particle concentration (NMR) were higher (1597 vs 1404 nmol/L; P= 0.0001) and LDL particle size (NMR) was lower (21.5 vs 21.8 nm; P=0.046) among women who subsequently had cardiovascular events (n=130) than among those who did not (n= 130). Of these 2 factors, LDL particle concentration (NMR) was the stronger predictor (relative risk for the highest compared with the lowest quartile=4.17, 95% CI 1.96-8.87). This compared with a relative risk of 3.11 (95% CI 1.55-6.26) for the ratio of total cholesterol to HDL cholesterol and a relative risk of 5.91 (95% CI 2.65-13.15) for C-reactive protein. The areas under the receiver operating characteristic curves for LDL particle concentration (NMR), total cholesterol to HDL cholesterol ratio, and C-reactive protein were 0.64, 0.64, and 0.66, respectively. LDL particle concentration (NMR) correlated with several traditionally assessed lipid and nonlipid risk factors, and thus adjustment for these tended to attenuate the magnitude of association between LDL particle concentration (NMR) and risk. CONCLUSIONS: In this cohort, LDL particle concentration measured by NMR spectroscopy was a predictor of future cardiovascular risk. However, the magnitude of predictive value of LDL particle concentration (NMR) was not substantively different from that of the total cholesterol to HDL cholesterol ratio and was less than that of C-reactive protein.

C-Reactive Protein↗
PubMed2002

Interrelationships among circulating interleukin-6, C-reactive protein, and traditional cardiovascular risk factors in women.

OBJECTIVE: Interleukin-6 (IL-6) and C-reactive protein (CRP) are markers of systemic vascular inflammation that herald atherothrombosis and may have important interrelationships with traditional cardiovascular risk factors. METHODS AND RESULTS: We conducted a cross-sectional analysis among 340 apparently healthy women enrolled in the Women's Health Study. In unadjusted analyses, higher levels of IL-6 and CRP were seen with increasing body mass index (BMI), systolic and diastolic blood pressure, and smoking exposure. IL-6 levels were related to the frequency of alcohol intake (P=0.002) and showed an inverse relationship with exercise frequency and hormone replacement therapy (P<0.0001 for both). CRP levels increased with hormone replacement therapy (P=0.0002). Associations among IL-6, CRP, and lipid levels were minimal. Overall, mean levels of IL-6 and CRP increased with increasing numbers of clinical risk factors (P<0.0001). In multivariate analyses, independent relationships were seen between levels of IL-6 and age, BMI, smoking, systolic blood pressure, alcohol use, presence of diabetes, and frequency of exercise. CRP was associated with age, BMI, systolic blood pressure, high density lipoprotein, smoking, and hormone replacement therapy in adjusted analyses. CONCLUSIONS: Plasma levels of IL-6 and CRP are independently related to several clinical cardiovascular risk factors in women.

Alcohol Drinking↗
PubMed2002

Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease: prospective analysis from the Women's Health Initiative observational study.

CONTEXT: Postmenopausal hormone replacement therapy (HRT) has been shown to elevate C-reactive protein (CRP) levels. Several inflammatory biomarkers, including CRP, are associated with increased cardiovascular risk. However, whether the effect of HRT on CRP represents a clinical hazard is unknown. OBJECTIVES: To assess the association between baseline levels of CRP and interleukin 6 (IL-6) and incident coronary heart disease (CHD) and to examine the relationship between baseline use of HRT, CRP, and IL-6 levels as they relate to subsequent vascular risk. DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-control study of postmenopausal women, forming part of the Women's Health Initiative, a large, nationwide, observational study. Among 75 343 women with no history of cardiovascular disease or cancer, 304 women who developed incident CHD were defined as cases and matched by age, smoking status, ethnicity, and follow-up time with 304 study participants who remained event free during a median observation period of 2.9 years. MAIN OUTCOME MEASURE: Incidence of first myocardial infarction or death from CHD. RESULTS: Median baseline levels of CRP (0.33 vs 0.25 mg/dL; interquartile range [IQR], 0.14-0.71 vs 0.10-0.47; P<.001) and IL-6 (1.81 vs 1.47 pg/mL; IQR, 1.30-2.75 vs 1.05-2.15; P<.001) were significantly higher among cases compared with controls. In matched analyses, the odds ratio (OR) for incident CHD in the highest vs lowest quartile was 2.3 for CRP (95% confidence interval [CI], 1.4-3.7; P for trend =.002) and 3.3 for IL-6 (95% CI, 2.0-5.5; P for trend <.001). After additional adjustment for lipid and nonlipid risk factors, both inflammatory markers were significantly associated with a 2-fold increase in odds for CHD events. As anticipated, current use of HRT was associated with significantly elevated median CRP levels. However, there was no association between HRT and IL-6. In analyses comparing individuals with comparable baseline levels of either CRP or IL-6, those taking or not taking HRT had similar CHD ORs. In analyses stratified by HRT, we observed a positively graded relationship between plasma CRP levels and the OR for CHD among both users and nonusers of HRT across the full spectrum of baseline CRP. CONCLUSIONS: These prospective findings indicate that CRP and IL-6 independently predict vascular events among apparently healthy postmenopausal women and that HRT increases CRP. However, use or nonuse of HRT had less importance as a predictor of cardiovascular risk than did baseline levels of either CRP or IL-6.

Aged↗
PubMed2002

Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men.

BACKGROUND: Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis. METHODS AND RESULTS: In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [P=0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [P=0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P(trend)=0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P(trend)=0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models. CONCLUSIONS: Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.

Adult↗
PubMed2002

The prognostic value of serum myoglobin in patients with non-ST-segment elevation acute coronary syndromes. Results from the TIMI 11B and TACTICS-TIMI 18 studies.

OBJECTIVES: The goal of this study was to define the prognostic value of serum myoglobin in patients with non-ST-elevation acute coronary syndromes (ACS). BACKGROUND: While myoglobin is useful for the early diagnosis of myocardial infarction (MI), its role in the early risk-stratification of patients with ACS has not been established. METHODS: Myoglobin, creatine kinase-MB subfraction (CK-MB) and troponin I (cTnI) were measured at randomization in 616 patients from the Thrombolysis In Myocardial Ischemia/Infarction (TIMI) 11B study and 1,841 patients from the Treat Angina with Aggrastat and Determine Cost of Therapy with an Invasive or Conservative Therapy-Thrombolysis In Myocardial Ischemia/Infarction (TACTICS-TIMI) 18 study. The risks for death and nonfatal MI through six months of follow-up were compared between patients with and without myoglobin elevation (>110 microg/l) in each study and in a dataset combining all eligible patients from both studies (n = 2,457). RESULTS: In a multivariate model adjusting for baseline characteristics, ST changes and CK-MB and cTnI levels, an elevated baseline myoglobin was associated with increased six-month mortality in TIMI 11B (adjusted odds ratio [OR] 2.9 [95% confidence interval [CI] 1.2 to 7.1]), TACTICS-TIMI 18 (adjusted OR 3.0 [95% CI 1.5 to 5.9]) and the combined dataset (adjusted OR 3.0 [95% CI 1.8 to 5.0]). In contrast, there was no significant association between myoglobin elevation and nonfatal MI (combined dataset adjusted OR 1.55, 95% CI 0.9 to 2.6). In TACTICS-TIMI 18, patients with versus those without myoglobin elevation were more likely to have an occluded culprit artery (28% vs. 10%; p < 0.0001) and visible thrombus (49% vs. 34%; p = 0.006) and less likely to have TIMI 3 flow (53% vs. 68%; p = 0.009). CONCLUSIONS: A serum concentration of myoglobin above the MI detection threshold (>110 microg/l) is associated with an increased risk of six-month mortality, independent of baseline clinical characteristics, electrocardiographic changes and elevation in CK-MB and cTnI. These findings suggest that myoglobin may be a useful addition to cardiac biomarker panels for early risk-stratification in ACS.

Acute Disease↗
PubMed2002

Prospective study of C-reactive protein, homocysteine, and plasma lipid levels as predictors of sudden cardiac death.

BACKGROUND: Sudden cardiac death (SCD) is an important cause of mortality even among apparently healthy populations. However, our ability to identify those at risk for SCD in the general population is poor, and more specific markers are needed. METHODS AND RESULTS: To compare and contrast the relative importance of C-reactive protein (CRP), homocysteine, and lipids as long-term predictors of SCD, we performed a prospective, nested, case-control analysis involving 97 cases of SCD among apparently healthy men enrolled in the Physician's Health Study. Of these plasma markers measured, only baseline CRP levels were significantly associated with the risk of SCD over the ensuing 17 years of follow-up (P for trend=0.001). The increase in risk associated with CRP levels was primarily seen among men in the highest quartile, who were at a 2.78-fold increased risk of SCD (95% CI 1.35 to 5.72) compared with men in the lowest quartile. These results were not significantly altered in analyses that (in addition to the matching variables of age and smoking status) controlled for lipid parameters, homocysteine, and multiple cardiac risk factors (relative risk for highest versus lowest quartile 2.65, 95% CI 0.79 to 8.83; P for trend=0.03). In contrast to the positive relationship observed for CRP, neither homocysteine nor lipid levels were significantly associated with risk of SCD. CONCLUSIONS: These prospective data suggest that CRP levels may be useful in identifying apparently healthy men who are at an increased long-term risk of SCD.

Adult↗
PubMed2002

Multimarker approach to risk stratification in non-ST elevation acute coronary syndromes: simultaneous assessment of troponin I, C-reactive protein, and B-type natriuretic peptide.

BACKGROUND: In patients with acute coronary syndromes (ACS), troponin I (TnI), C-reactive protein (CRP), and B-type natriuretic peptide (BNP) each predict adverse cardiac events. Little is known, however, about the utility of these biomarkers in combination. METHODS AND RESULTS: Baseline measurements of TnI, CRP, and BNP were performed in 450 patients in OPUS-TIMI 16. Elevations in TnI, CRP, and BNP each were independent predictors of the composite of death, myocardial infarction (MI), or congestive heart failure (CHF). When patients were categorized on the basis of the number of elevated biomarkers at presentation, there was a near doubling of the mortality risk for each additional biomarker that was elevated (P=0.01). Similar relationships existed for the endpoints of MI, CHF, and the composite, both at 30 days and through 10 months. In a validation cohort of 1635 patients in TACTICS-TIMI 18, the number of elevated biomarkers remained a significant predictor of the composite endpoint after adjustment for known clinical predictors: patients with one, two, and three elevated biomarkers had a 2.1- (P=0.006), 3.1- (P<0.001), and 3.7- (P=0.001) fold increase in the risk of death, MI, or CHF by 6 months. CONCLUSIONS: Troponin, CRP, and BNP each provide unique prognostic information in patients with ACS. A simple multimarker strategy that categorizes patients based on the number of elevated biomarkers at presentation allows risk stratification over a broad range of short- and long-term major cardiac events.

Acute Disease↗
PubMed2002

Is C-reactive protein specific for vascular disease in women?

BACKGROUND: C-reactive protein (CRP) predicts risk for future cardiovascular events in asymptomatic individuals. However, because CRP also predicts total mortality, its specificity for vascular disease is uncertain. OBJECTIVE: To compare the predictive value of CRP for cancer and cardiovascular disease, the major determinants of mortality. DESIGN: Prospective, nested case-control study. SETTING: The Women's Health Study, an ongoing prospective cohort study involving 28345 U.S. women 45 years of age and older who were healthy at the time of enrollment. PARTICIPANTS: 643 women who subsequently developed cancer or had cardiovascular events; 643 age- and smoking-matched women who remained free of either disease during 58-month follow-up. MEASUREMENTS: Baseline CRP levels. RESULTS: Little evidence showed that increasing quartiles of baseline CRP predicted incident cancer (adjusted relative risks, 1.0, 1.2, 1.1, and 1.3; P for trend > 0.2). In contrast, increasing quartiles of baseline CRP were a strong marker of risk for future cardiovascular disease (adjusted relative risks, 1.0, 2.9, 3.4, and 5.6; P for trend < 0.001). CONCLUSION: C-reactive protein appears to independently predict cardiovascular events but not cancer.

Biomarkers↗
PubMed2002

C-reactive protein and cardiovascular disease: a review of risk prediction and interventions.

BACKGROUND: Coronary vascular disease (CVD) has a high prevalence in the United States, yet 40-50% of those with that diagnosis have normal or mildly increased cholesterol levels. Increased C-reactive protein (CRP) has been associated with CVD, in those presenting after an acute coronary event, and also in apparently healthy individuals. METHODS: We reviewed the literature on this association, and on the relationship between CRP and traditional CVD risk factors including smoking, hypertension, cholesterol and obesity. Also examined is the effect of various medications used in patients with CVD on CRP concentrations. RESULTS: CRP correlates with risk of CVD in patients who have a history of acute coronary disease, stable angina, and in those who have never been diagnosed with CVD. CRP imparts risk that is independent of hyperlipidemia. CONCLUSION: Once commercially available CRP assays are shown to be reliable, CRP may help predict short- and long-term cardiovascular outcomes and may have a role in CVD screening analogous to that of lipid. In the future CRP may modify treatment and preventive therapies.

Age Factors↗
PubMed2002

High sensitivity C-reactive protein: an emerging role in cardiovascular risk assessment.

Coronary heart disease (CHD) is the major cause of death in the developed world and screening for conventional cardiovascular risk factors fails to identify more than 50% of the individuals who will present with acute coronary syndromes. Chronic inflammation appears to play a significant role in the initiation and development of atherosclerosis. Recent investigations have shown an association between inflammatory markers such as C-reactive protein (CRP) and CHD. These markers have proven useful as prognostic indicators in acute coronary syndromes and in predicting future coronary events in apparently healthy men and women. The availability of high sensitivity CRP (hs-CRP) assays has been crucial in exploring the role of this acute phase reactant in primary prevention settings. In this review, we discuss the evidence associating these inflammatory markers, especially CRP, with the pathogenesis of atherosclerosis and acute coronary syndromes, and we address the mechanism of risk as well as the clinical utility of this marker.

Biomarkers↗
PubMed2002

Frequent intake of tropical fruits that are rich in beta-cryptoxanthin is associated with higher plasma beta-cryptoxanthin concentrations in Costa Rican adolescents.

Dietary tocopherols and carotenoids may play a role in preventing cancer and cardiovascular diseases. Because these may begin to develop during adolescence, dietary patterns during this period could influence long-term risk. The objective of this study was to examine the intake and plasma concentrations of the major carotenoids and tocopherols in 159 adolescents (mean +/- SD, 15.5 +/- 2.5 y old) living in Costa Rica. All participants completed a 135-item food-frequency questionnaire and provided a fasting blood sample. Carotenoid and tocopherol intakes were adjusted for total energy and plasma concentrations for total cholesterol. The relative abundance of carotenoids in the diet was similar to their distribution in plasma; lycopene was the most abundant, followed by beta-carotene and lutein + zeaxanthin. gamma-Tocopherol was more abundant than alpha-tocopherol in the diet, but alpha-tocopherol was approximately sevenfold higher in plasma. The highest diet-plasma correlations (adjusted for age, sex and body mass index) were 0.38 for beta-cryptoxanthin, 0.33 for gamma-tocopherol and 0.17 for lutein + zeaxanthin (all P < 0.05). All other correlations were r < 0.15. Papaya intake was the best food predictor of plasma beta-cryptoxanthin concentrations (r = 0.41). Subjects that frequently (> or =3/d) consumed tropical fruits with at least 50 micro g/100 g beta-cryptoxanthin (papaya, tangerine, orange and watermelon) had twofold the plasma beta-cryptoxanthin concentrations of those with intakes of <4/wk (P for trend = 0.0009). In sum, the diet-plasma carotenoid and tocopherol correlations were generally low in Costa Rican adolescents. Intakes of beta-cryptoxanthin and papaya, a tropical fruit frequently consumed in Latin America, were the best predictors of beta-cryptoxanthin concentrations in plasma.

Adolescent↗
PubMed2002

Measurement of whole blood sirolimus by an HPLC assay using solid-phase extraction and UV detection.

The authors developed an HPLC assay for determining blood sirolimus concentration using a relatively simple solid-phase extraction and UV detection. The retention times of sirolimus and the internal standard, 32-desmethoxyrapamycin, are 8.7 and 9.3 minutes, respectively. The assay possesses linearity up to 200 ng/mL, sensitivity to 2.0 ng/mL, and day-to-day reproducibility of 8.8, 9.8, 6.1, and 6.4% at sirolimus concentrations of 6, 10, 20, and 30 ng/mL, respectively. A patient correlation study using this HPLC method and an established LC/MS/MS assay revealed a slope of 0.982 and intercept of -0.021 ng/mL and a correlation coefficient of 0.99 (n = 37). Of the 31 different drugs tested none interfered with the measurement of the drug of interest, and a recovery study gave an overall mean recovery of 101.8%. The authors conclude that the method described here is suited for the therapeutic monitoring of blood sirolimus concentration.

Chromatography, High Pressure Liquid↗
PubMed2002

Inflammatory markers and coronary heart disease.

PURPOSE OF REVIEW: Despite changes in lifestyle and the use of effective pharmacologic interventions to lower cholesterol levels, coronary heart disease remains the major cause of morbidity and mortality in the developed world. Cholesterol screening fails to identify almost 50% of those individuals who will present with acute coronary syndromes. Recent evidence from laboratory and prospective clinical studies demonstrates that atherosclerosis is not simply a disease of lipid deposition, but rather is an inflammatory process with highly specific cellular and molecular responses. The clinical utility of inflammatory markers has been examined in a variety of atherothrombotic diseases. Because C-reactive protein is highly stable in stored frozen samples, and automated and robust analytical systems for its measurement are available, it has become the most widely examined inflammatory marker. RECENT FINDINGS: C-reactive protein has consistently been shown to be a useful prognostic indicator in acute coronary syndromes and is a strong predictor of future coronary events in apparently healthy individuals. In addition, C-reactive protein can identify individuals with normal lipid levels who are at increased risk for future coronary events. Because drugs such as aspirin and statins reduce inflammatory risk, C-reactive protein has the potential to guide the use of these therapies in high-risk individuals for primary prevention. SUMMARY: C-reactive protein may have a role in global risk assessment for primary prevention and in targeting those patients who will benefit from anti-inflammatory therapies. In addition, it may also be a good prognostic indicator in patients with acute coronary syndromes.

Biomarkers↗
PubMed2002

Longitudinal association of glycemia and microalbuminuria: the Framingham Offspring Study.

OBJECTIVE: To assess current and long-term associations of glycemia with microalbuminuria, a marker of generalized endothelial injury. RESEARCH DESIGN AND METHODS: We measured clinical characteristics, fasting plasma glucose, and the urinary albumin-to-creatinine ratio (UACR) in 1,311 men and 1,518 women attending the sixth examination cycle (1995-1998) of the Framingham Offspring Study. After excluding participants with diabetes or cardiovascular disease (CVD) at the baseline examination (1971-1974), we used fasting glucose measured at baseline, examination 6, and at least two additional examinations from 1974 to 1995 in regression models to predict risk for microalbuminuria (UACR > or = 30 mg/g) associated with baseline, current, and 24-year time-integrated glycemia. RESULTS: Microalbuminuria was present in 9.5% of men and 13.4% of women. Among men, age-adjusted odds ratios (95% CI) for microalbuminuria associated with each 0.28 mmol/l (5 mg/dl) increase in baseline, current, and time-integrated glucose levels were 1.12 (1.00-1.16), 1.08 (1.05-1.10), and 1.16 (1.11-1.21), respectively. These effects persisted after adjustment for systolic blood pressure and other confounders. Higher glucose levels also predicted incident diabetes and CVD. Mean time-integrated glucose levels were highest among men who developed both CVD and microalbuminuria (SE 6.82 +/- 0.16 mmol/l), intermediate among men with either condition (6.03 +/- 0.65 mmol/l), and lowest among men with neither condition (5.49 +/- 0.02 mmol/l; P < 0.001 for all pairwise comparisons). We observed similar associations in women. CONCLUSIONS: Long-term hyperglycemia and subdiabetic glycemia increase risk for microalbuminuria. Microalbuminuria, type 2 diabetes, and CVD seem to arise together over the course of decades, consistent with the hypothesis that they share a common antecedent.

Aged↗