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Nader Rifai

Publications and source records attributed to Nader Rifai.

At least 73 records · Page 4Linked to original sources

Prevalence of the metabolic syndrome in American adolescents: findings from the Third National Health and Nutrition Examination Survey.

BACKGROUND: Metabolic syndrome (MetS) is defined by the Third Report of the Adult Treatment Panel (ATP III) using criteria easily applied by clinicians and researchers. There is no standard pediatric definition. METHODS AND RESULTS: We defined pediatric MetS using criteria analogous to ATP III as > or =3 of the following: (1) fasting triglycerides > or =1.1 mmol/L (100 mg/dL); (2) HDL <1.3 mmol/L (50 mg/dL), except in boys aged 15 to 19 years, in whom the cutpoint was <1.2 mmol/L (45 mg/dL); (3) fasting glucose > or =6.1 mmol/L (110 mg/dL); (4) waist circumference >75th percentile for age and gender; and (5) systolic blood pressure >90th percentile for gender, age, and height. MetS prevalence in US adolescents was estimated with the Third National Health and Nutritional Survey 1988 to 1994. Among 1960 children aged > or =12 years who fasted > or =8 hours, two thirds had at least 1 metabolic abnormality, and nearly 1 in 10 had MetS. The racial/ethnic distribution was similar to adults: Mexican-Americans, followed by non-Hispanic whites, had a greater prevalence of MetS compared with non-Hispanic blacks (12.9%, [95% CI 10.4% to 15.4%]; 10.9%, [95% CI 8.4% to 13.4%]; and 2.5%, [95% CI 1.3% to 3.7%], respectively). Nearly one third (31.2% [95% CI 28.3% to 34.1%]) of overweight/obese adolescents had MetS. CONCLUSIONS: Our definition of pediatric MetS, designed to be closely analogous to ATP III, found MetS is common in adolescents and has a similar racial/ethnic distribution to adults in this representative national sample. Because childhood MetS likely tracks into adulthood, early identification may help target interventions to improve future cardiovascular health.

Adolescent↗

Quality specifications and the assessment of the biochemical risk of atherosclerosis.

BACKGROUND: Coronary heart disease (CHD) is the major cause of death in the western world and biochemical markers have been used to identify those individuals who are at increased risk. Although numerous markers have been considered, only total, low-density lipoprotein (LDL), and high-density lipoprotein cholesterol, triglyceride and C-reactive protein (CRP) have been recommended for assessing CHD risk in routine clinical practice. METHODS: Specific performance goals have been established for the lipid markers and for the measurement of CRP considering both some significant pre-analytical and analytical issues which could affect the quality of their measurements. RESULTS: The target for quality specifications for LDL-C with the reference method are CV < or =4% and bias < or =4%. Regarding the measurement of CRP, total imprecision should be <10% across the linear range of the assay and the analytical sensitivity may allow a reliable measurement at values lower than 0.3 mg/l. CONCLUSIONS: Although national guidelines do exist for LDL-C measurement, additional studies are needed to better characterize the performances of routine methods. As more data are available for CRP, guidelines for its measurement will be soon developed.

Arteriosclerosis↗

B-type natriuretic peptide at presentation and prognosis in patients with ST-segment elevation myocardial infarction: an ENTIRE-TIMI-23 substudy.

OBJECTIVES: We sought to evaluate B-type natriuretic peptide (BNP), alone and in comparison to cardiac troponin I (cTnI) and high-sensitivity C-reactive protein (hs-CRP), for risk assessment at initial presentation with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Elevated levels of BNP drawn two to four days after acute myocardial infarction are associated with higher mortality. Sparse data are available on its use at first presentation with STEMI. METHODS: We obtained samples from 438 patients presenting within 6 h of STEMI enrolled in the Enoxaparin Tenecteplase-Tissue-Type Plasminogen Activator With or Without Glycoprotein IIb/IIIa Inhibitor as Reperfusion Strategy in ST-Segment Elevation Myocardial Infarction (ENTIRE)-Thrombolysis In Myocardial Infarction (TIMI)-23 trial. Outcomes were assessed through 30 days. RESULTS: Median BNP was higher in patients who died (89 pg/ml, 25th to 75th percentile: 40 to 192), compared with survivors (15 pg/ml, 25th to 75th percentile: 8.8 to 32, p < 0.0001). Patients with BNP >80 pg/ml were at significantly higher risk of death (17.4% vs. 1.8%, p < 0.0001). Cardiac troponin established a gradient of mortality between the highest and lowest quartile (7.9% vs. 0%, p = 0.007). C-reactive protein was not associated with outcome. After adjustment for cTnI, hs-CRP, and major clinical predictors, including age, heart failure, anterior myocardial infarction location, heart rate, and blood pressure, a BNP level >80 pg/ml was associated with a seven-fold higher mortality risk (odds ratio 7.2, 95% confidence interval 2.1 to 24.5, p = 0.001). Patients with BNP >80 pg/ml were also more likely to have impaired coronary flow (p = 0.049) and incomplete resolution of ST-segment elevation (p = 0.05). CONCLUSIONS: Increased concentrations of BNP at initial presentation of patients with STEMI are associated with impaired reperfusion after fibrinolysis and higher short-term risk of mortality. These data support the value of combining markers of hemodynamic stress with traditional approaches to risk assessment in acute myocardial infarction.

Adult↗

Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study.

BACKGROUND: Patients with acute coronary syndromes have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit CD40L signaling in vitro, but there are no prospective studies of statins and sCD40L in acute coronary syndromes. METHODS AND RESULTS: We measured sCD40L in subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16 weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) at 16 weeks. Odds ratios (ORs) and 95% CIs from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0.08). CONCLUSIONS: In patients with acute coronary syndromes, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Early statin therapy after acute coronary syndromes counters the risk associated with elevated sCD40L.

Aged↗

The effect of dexrazoxane on myocardial injury in doxorubicin-treated children with acute lymphoblastic leukemia.

BACKGROUND: Doxorubicin chemotherapy is very effective in children with acute lymphoblastic leukemia (ALL) but also injures myocardial cells. Dexrazoxane, a free-radical scavenger, may protect the heart from doxorubicin-associated damage. METHODS: To determine whether dexrazoxane decreases doxorubicin-associated injury of cardiomyocytes, we randomly assigned 101 children with ALL to receive doxorubicin alone (30 mg per square meter of body-surface area every three weeks for 10 doses) and 105 to receive dexrazoxane (300 mg per square meter) followed immediately by doxorubicin. Serial measurements of serum cardiac troponin T were obtained in 76 of 101 patients in the doxorubicin group and 82 of 105 patients in the group given dexrazoxane and doxorubicin. A total of 2377 serum samples (mean, 15.1 samples per patient) were obtained before, during, and after treatment with doxorubicin. Troponin T levels were evaluated in a blinded fashion to determine whether they were elevated (>0.01 ng per milliliter)--the primary end point--or extremely elevated (>0.025 ng per milliliter). RESULTS: Elevations of troponin T occurred in 35 percent of the patients (55 of 158). Patients treated with doxorubicin alone were more likely than those who received dexrazoxane and doxorubicin to have elevated troponin T levels (50 percent vs. 21 percent, P<0.001) and extremely elevated troponin T levels (32 percent vs. 10 percent, P<0.001). The median follow-up was 2.7 years. The rate of event-free survival at 2.5 years was 83 percent in both groups (P=0.87 by the log-rank test). CONCLUSIONS: Dexrazoxane prevents or reduces cardiac injury, as reflected by elevations in troponin T, that is associated with the use of doxorubicin for childhood ALL without compromising the antileukemic efficacy of doxorubicin. Longer follow-up will be necessary to determine the influence of dexrazoxane on echocardiographic findings at four years and on event-free survival.

Antibiotics, Antineoplastic↗

Serum aldosterone and the incidence of hypertension in nonhypertensive persons.

BACKGROUND: Primary hyperaldosteronism is a well-recognized cause of secondary hypertension. It is unknown whether serum aldosterone levels within the physiologic range influence the risk of hypertension. METHODS: We investigated the relation of baseline serum aldosterone levels to increases in blood pressure and the incidence of hypertension after four years in 1688 nonhypertensive participants in the Framingham Offspring Study (mean age, 55 years), 58 percent of whom were women. We defined an increase in blood pressure as an increment of at least one blood-pressure category (as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) and defined hypertension as a systolic blood pressure of 140 mm Hg or higher, a diastolic blood pressure of 90 mm Hg or higher, or the use of antihypertensive medications. RESULTS: At follow-up, the blood-pressure category had increased in 33.6 percent of the participants, and hypertension had developed in 14.8 percent. In multivariable models, a 16 percent increase in the risk of an elevation in blood pressure (P=0.002) and a 17 percent increase in the risk of hypertension (P=0.03) were observed per quartile increment in the serum aldosterone level. The highest serum aldosterone quartile, relative to the lowest, was associated with a 1.60-fold risk of an elevation in blood pressure (95 percent confidence interval, 1.19 to 2.14) and a 1.61-fold risk of hypertension (95 percent confidence interval, 1.05 to 2.46). The associations between the serum aldosterone level and blood-pressure outcomes were not significantly affected by adjustment for urinary sodium excretion or left ventricular thickness or internal dimensions. CONCLUSIONS: In our community-based sample, increased aldosterone levels within the physiologic range predisposed persons to the development of hypertension.

Aldosterone↗

No association between pre-diagnostic plasma C-reactive protein concentration and subsequent prostate cancer.

BACKGROUND: We evaluated the association of pre-diagnostic plasma concentration of C-reactive protein, a sensitive, but non-specific indicator of inflammation, with subsequent risk of prostate cancer. METHODS: Included were 264 histologically confirmed prostate cancer cases and 264 age-matched controls who were participants in the CLUE II cohort of Washington County, MD. C-reactive protein was measured using a high-sensitivity immunoturbidimetric assay. Odds ratios (ORs) and 95% confidence intervals (CI) were estimated from conditional logistic regression models by fourth of the C-reactive protein distribution with cutpoints based on the controls. The median concentrations from the lowest to highest fourth were 0.41, 1.03, 1.90, and 4.53 mg/L. RESULTS: Geometric mean plasma concentrations did not differ between the cases (1.24 +/- 2.94 mg/L) and controls (1.41 +/- 2.97 mg/L; P = 0.16). Compared to the bottom fourth, the ORs (95% CI) of prostate cancer were 1.29 (0.80-2.08), 0.98 (0.61-1.58), and 0.95 (0.57-1.58) for the second, third, and highest fourths (P trend = 0.66). These findings were unchanged after adjusting for body mass index (BMI) and cigarette smoking status or after excluding men with markedly elevated C-reactive protein, cases diagnosed during the first 2 years of follow-up, or controls who never had a PSA test. These findings did not differ by stage or grade of prostate cancer. CONCLUSIONS: Pre-diagnostic plasma concentration of C-reactive protein was not associated with subsequent risk of prostate cancer.

Aged↗

Apolipoprotein(a) size and lipoprotein(a) concentration and future risk of angina pectoris with evidence of severe coronary atherosclerosis in men: The Physicians' Health Study.

BACKGROUND: The relationship of lipoprotein (a) [Lp(a)] concentrations with risk of coronary heart disease needs clarification, especially for threshold values for increased risk and for possible interactions with LDL-cholesterol concentrations and apolipoprotein (a) [apo(a)] size polymorphism. This study was designed to examine the ability of baseline Lp(a) concentration and apo(a) size to predict future severe angina pectoris in apparently healthy men. METHODS: Baseline Lp(a) concentration and apo(a) size were determined in 195 men who subsequently developed angina and in 195 men who remained free of cardiovascular disease for 5 years. RESULTS: Cases had higher median Lp(a) concentrations than did controls (30.6 vs 22.5 nmol/L; P = 0.02). Lp(a) concentration was predictive of angina [relative risk (RR) from lowest to highest quintiles: 1.0, 1.5, 1.0, 1.8, and 2.6; P for trend = 0.015]. The increased risk was approximately 4-fold (95% confidence interval, 1.4- to 11-fold) among men who had Lp(a) above the 95th percentile (>158 nmol/L). Men with Lp(a) concentrations in the highest quintile and LDL-cholesterol concentrations >1600 mg/L had a 12-fold increased risk (95% confidence interval, 1.5- to 43-fold). Small apo(a) size isoforms also significantly predicted risk of angina (RR for lowest quintile = 4.1; P for trend = 0.004). When the independent effect of Lp(a) concentration and apo(a) size was assessed by including them in the same multivariate model, only the association between apo(a) size and risk remained significant. CONCLUSIONS: High Lp(a) predicts risk of angina, and the risk is substantially increased with high concomitant LDL-cholesterol. Small apo(a) size predicts angina with greater strength and independence than Lp(a) concentration.

Adult↗

Biomarkers of endothelial dysfunction and risk of type 2 diabetes mellitus.

CONTEXT: Endothelial dysfunction occurs in diagnosed type 2 diabetes mellitus but may also precede development of diabetes. OBJECTIVE: To determine whether elevated plasma levels of biomarkers reflecting endothelial dysfunction (E-selectin; intercellular adhesion molecule 1 [ICAM-1]; and vascular cell adhesion molecule 1 [VCAM-1]) predict development of type 2 diabetes in initially nondiabetic women. DESIGN AND SETTING: Prospective, nested case-control study within the Nurses' Health Study, an ongoing US study initiated in 1976. PARTICIPANTS: Of 121 700 women initially enrolled, 32 826 provided blood samples in 1989-1990; of those free of diabetes, cardiovascular disease, or cancer at baseline, 737 developed incident diabetes by 2000. Controls (n = 785) were selected according to matched age, fasting status, and race. MAIN OUTCOME MEASURE: Risk of confirmed clinically diagnosed type 2 diabetes by baseline levels of E-selectin, ICAM-1, and VCAM-1. RESULTS: Baseline median levels of the biomarkers were significantly higher among cases than among controls (E-selectin, 61.2 vs 45.4 ng/mL; ICAM-1, 264.9 vs 247.0 ng/mL; VCAM-1, 545.4 vs 526.0 ng/mL [all P values < or =.004]). Elevated E-selectin and ICAM-1 levels predicted incident diabetes in logistic regression models conditioned on matching criteria and adjusted for body mass index (BMI), family history of diabetes, smoking, diet score, alcohol intake, activity index, and postmenopausal hormone use. The adjusted relative risks for incident diabetes in the top quintile vs the bottom quintiles were 5.43 for E-selectin (95% confidence interval [CI], 3.47-8.50), 3.56 for ICAM-1 (95% CI, 2.28-5.58), and 1.12 for VCAM-1 (95% CI, 0.76-1.66). Adjustment for waist circumference instead of BMI or further adjustment for baseline levels of C-reactive protein, fasting insulin, and hemoglobin A(1c) or exclusion of cases diagnosed during the first 4 years of follow-up did not alter these associations. CONCLUSION: Endothelial dysfunction predicts type 2 diabetes in women independent of other known risk factors, including obesity and subclinical inflammation.

Adult↗

Plasma adiponectin levels and risk of myocardial infarction in men.

CONTEXT: Adiponectin, a recently discovered adipocyte-derived peptide, is involved in the regulation of insulin sensitivity and lipid oxidation and, purportedly, in the development of atherosclerosis and coronary heart disease in humans. OBJECTIVE: To assess prospectively whether plasma adiponectin concentrations are associated with risk of myocardial infarction (MI). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study among 18 225 male participants of the Health Professionals Follow-up Study aged 40 to 75 years who were free of diagnosed cardiovascular disease at the time of blood draw (1993-1995). During 6 years of follow-up through January 31, 2000, 266 men subsequently developed nonfatal MI or fatal coronary heart disease. Using risk set sampling, controls were selected in a 2:1 ratio matched for age, date of blood draw, and smoking status (n = 532). MAIN OUTCOME MEASURE: Incidence of nonfatal MI and fatal coronary heart disease by adiponectin level. RESULTS: After adjustment for matched variables, participants in the highest compared with the lowest quintile of adiponectin levels had a significantly decreased risk of MI (relative risk [RR], 0.39; 95% confidence interval [CI], 0.23-0.64; P for trend <.001). Additional adjustment for family history of MI, body mass index, alcohol consumption, physical activity, and history of diabetes and hypertension did not substantively affect this relationship (RR, 0.41; 95% CI, 0.24-0.70; P for trend <.001). Further adjustment for hemoglobin A1c or C-reactive protein levels also had little impact, but additional adjustment for low- and high-density lipoprotein cholesterol levels modestly attenuated this association (RR, 0.56; 95% CI, 0.32-0.99; P for trend =.02). CONCLUSIONS: High plasma adiponectin concentrations are associated with lower risk of MI in men. This relationship can be only partly explained by differences in blood lipids and is independent of inflammation and glycemic status.

Adiponectin↗

Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk.

OBJECTIVES: We sought to investigate the effects of sleep loss on high-sensitivity C-reactive protein (CRP) levels. BACKGROUND: Concentrations of high-sensitivity CRP are predictive of future cardiovascular morbidity. In epidemiologic studies, short sleep duration and sleep complaints have also been associated with increased cardiovascular morbidity. Two studies were undertaken to examine the effect of acute total and short-term partial sleep deprivation on concentrations of high-sensitivity CRP in healthy human subjects. METHODS: In Experiment 1, 10 healthy adult subjects stayed awake for 88 continuous hours. Samples of high-sensitivity CRP were collected every 90 min for 5 consecutive days, encompassing the vigil. In Experiment 2, 10 subjects were randomly assigned to either 8.2 h (control) or 4.2 h (partial sleep deprivation) of nighttime sleep for 10 consecutive days. Hourly samples of high-sensitivity CRP were taken during a baseline night and on day 10 of the study protocol. RESULTS: The CRP concentrations increased during both total and partial sleep deprivation conditions, but remained stable in the control condition. Systolic blood pressure increased across deprivation in Experiment 1, and heart rate increased in Experiment 2. CONCLUSIONS: Both acute total and short-term partial sleep deprivation resulted in elevated high-sensitivity CRP concentrations, a stable marker of inflammation that has been shown to be predictive of cardiovascular morbidity. We propose that sleep loss may be one of the ways that inflammatory processes are activated and contribute to the association of sleep complaints, short sleep duration, and cardiovascular morbidity observed in epidemiologic surveys.

Adult↗

Long-term effect of combined vitamins E and C on coronary and peripheral endothelial function.

OBJECTIVES: We tested whether long-term administration of antioxidant vitamins C and E improves coronary and brachial artery endothelial function in patients with coronary artery disease (CAD). BACKGROUND: Endothelial function is a sensitive indicator of vascular health. Oxidant stress and oxidized low-density lipoprotein (LDL) impair endothelial function by reducing nitric oxide bioavailability in the artery wall. METHODS: We randomly assigned 30 subjects with CAD to combined vitamin E (800 IU per day) and C (1000 mg per day) or to placebos in a double-blind trial. Coronary artery endothelial function was measured as the change in coronary artery diameter to acetylcholine infusions (n = 18 patients), and brachial artery endothelial function was assessed by flow-mediated dilation (n = 25 patients) at baseline and six months. Plasma markers of oxidant stress (oxidized LDL and autoantibodies) were also measured. RESULTS: Plasma alpha-tocopherol (p < 0.001) and ascorbic acid (p < 0.02) increased with active therapy. Compared to placebo, there was no improvement in coronary and brachial endothelial vasomotor function over six months. Although vitamins C and E tended to reduce F2-isoprostanes (p = 0.065), they failed to alter oxidized LDL or autoantibodies to oxidized LDL. CONCLUSIONS: Long-term oral vitamins C and E do not improve key mechanisms in the biology of atherosclerosis or endothelial dysfunction, or reduce LDL oxidation in vivo.

Antioxidants↗

Association between C-reactive protein and age-related macular degeneration.

CONTEXT: C-reactive protein (CRP) is a systemic inflammatory marker associated with risk for cardiovascular disease (CVD). Some risk factors for CVD are associated with age-related macular degeneration (AMD), but the association between CRP and AMD is unknown. OBJECTIVE: To test the hypothesis that elevated CRP levels are associated with an increased risk for AMD. DESIGN, SETTING, AND PARTICIPANTS: A total of 930 (91%) of 1026 participants at 2 centers in the Age-Related Eye Disease Study (AREDS), a multicenter randomized trial of antioxidant vitamins and minerals, were enrolled in this case-control study. There were 183 individuals without any maculopathy, 200 with mild maculopathy, 325 with intermediate disease, and 222 with advanced AMD (geographic atrophy or neovascular AMD). The AMD status was assessed by standardized grading of fundus photographs, and stored fasting blood specimens drawn between January 1996 and April 1997 were analyzed for high-sensitivity CRP levels. MAIN OUTCOME MEASURE: Association between CRP and AMD. RESULTS: The CRP levels were significantly higher among participants with advanced AMD (case patients) than among those with no AMD (controls; median values, 3.4 vs 2.7 mg/L; P =.02). After adjustment for age, sex, and other variables, including smoking and body mass index, CRP levels were significantly associated with the presence of intermediate and advanced stages of AMD. The odds ratio (OR) for the highest vs the lowest quartile of CRP was 1.65 (95% confidence interval [CI], 1.07-2.55; P for trend =.02). The OR for CRP values at or above the 90th percentile (10.6 mg/L) was 1.92 (95% CI, 1.20-3.06), and the OR for CRP values at or above the mean plus 2 SDs (16.8 mg/L) was 2.03 (95% CI, 1.03-4.00). A trend for an increased risk for intermediate and advanced AMD with higher levels of CRP was seen for smokers (OR, 2.16; 95% CI, 1.33-3.49) and those who never smoked (OR, 2.03; 95% CI, 1.19-3.46) with the highest level of CRP. CONCLUSION: Our results suggest that elevated CRP level is an independent risk factor for AMD and may implicate the role of inflammation in the pathogenesis of AMD.

Aged↗

Body iron stores in relation to risk of type 2 diabetes in apparently healthy women.

CONTEXT: Type 2 diabetes is a common manifestation of hemochromatosis, a disease of iron overload. However, it is not clear whether higher iron stores predict the development of type 2 diabetes in a healthy population. OBJECTIVE: To examine plasma ferritin concentration and the ratio of the concentrations of transferrin receptors to ferritin in relation to risk of type 2 diabetes. DESIGN, SETTING, AND PARTICIPANTS: Prospective nested case-control study within the Nurses' Health Study cohort. Of the 32 826 women who provided blood samples during 1989-1990 and were free of diagnosed diabetes, cardiovascular disease, and cancer, 698 developed diabetes during 10 years of follow-up. The controls (n = 716) were matched to cases on age, race, and fasting status; and on body mass index (BMI) for cases in the top BMI decile. MAIN OUTCOME MEASURE: Incident cases of type 2 diabetes. RESULTS: Among cases, the mean (SD) concentration of ferritin was significantly higher (109 [105] vs 71.5 [68.7] ng/mL for controls; P<.001 for difference) and the mean (SD) ratio of transferrin receptors to ferritin was significantly lower (102 [205] vs 141 [340], respectively; P =.01). In conditional logistic regression stratified on the matching factors and controlled for BMI and other diabetes risk factors, the multivariate relative risks [RRs] of incident type 2 diabetes across increasing quintiles of ferritin were 1.00, 1.09 (95% confidence interval [CI], 0.70-1.70), 1.26 (95% CI, 0.82-1.95), 1.30 (95% CI, 0.83-2.04), and 2.68 (95% CI, 1.75-4.11) (P<.001 for trend). The RRs across increasing quintiles of transferrin receptors to ferritin ratio were 2.44 (95% CI, 1.61-3.71), 1.00 (95% CI, 0.64-1.56), 1.13 (95% CI, 0.73-1.74), 0.99 (95% CI, 0.64-1.53), and 1.00 (P =.01 for trend). Further adjustment for an inflammatory marker (C-reactive protein) did not change the results appreciably. The associations persisted within strata defined by levels of BMI, menopausal status, alcohol consumption, and C-reactive protein. CONCLUSION: Higher iron stores (reflected by an elevated ferritin concentration and a lower ratio of transferrin receptors to ferritin) are associated with an increased risk of type 2 diabetes in healthy women independent of known diabetes risk factors.

Adult↗

Differential expression of cardiac biomarkers by gender in patients with unstable angina/non-ST-elevation myocardial infarction: a TACTICS-TIMI 18 (Treat Angina with Aggrastat and determine Cost of Therapy with an Invasive or Conservative Strategy-Thrombolysis In Myocardial Infarction 18) substudy.

BACKGROUND: Diagnosis of coronary artery disease in women is more difficult because of lower specificity of symptoms and diagnostic accuracy of noninvasive testing. We sought to examine the relationship between gender and cardiac biomarkers in patients with unstable angina (UA)/non-ST-segment elevation myocardial infarction (NSTEMI). METHODS AND RESULTS: In the TACTICS-TIMI 18, OPUS-TIMI 16, and TIMI 11 studies, baseline samples were analyzed in the Thrombolysis In Myocardial Infarction (TIMI) biomarker core laboratory. We examined the relationship between gender and elevated biomarkers. Of 1865 patients from TACTICS-TIMI 18, 34% were women. Fewer women had elevated creatine kinase-MB or troponins, whereas more had elevated high-sensitivity C-reactive protein or brain natriuretic peptide. Presence of ST-segment deviation and TIMI risk scores were not significantly different. This pattern was confirmed in TIMI 11 and OPUS-TIMI 16. The prognostic value of the markers in TACTICS-TIMI 18 was similar in women and men. When a multimarker approach was examined, a greater proportion of high-risk women were identified. Marker-positive patients of both genders had improved outcome with an invasive strategy; however, marker-negative women appeared to have improved outcomes with a conservative strategy. CONCLUSIONS: In patients with UA/NSTEMI, there was a different pattern of presenting biomarkers. Men were more likely to have elevated creatine kinase-MB and troponins, whereas women were more likely to have elevated C-reactive protein and brain natriuretic peptide. This suggests that a multimarker approach may aid the initial risk assessment of UA/NSTEMI, especially in women. Further research is necessary to elucidate whether gender-related pathophysiological differences exist in presentation with acute coronary syndromes.

Acute Disease↗

C-reactive protein and the risk of incident colorectal cancer.

CONTEXT: Inflammation may play a role in the pathogenesis of colorectal cancer; however, epidemiological evidence supporting this hypothesis in average-risk persons is sparse. OBJECTIVE: To determine the risk of incident colon and rectal cancer associated with elevated baseline plasma concentrations of C-reactive protein (CRP). DESIGN, SETTING, AND PARTICIPANTS: Prospective, nested case-control study of a cohort of 22 887 adults (>18 years and Washington County, Maryland, residents) enrolled between May and October 1989 and followed up through December 2000. A total of 172 colorectal cancer cases were identified through linkage with the Washington County and Maryland State Cancer registries. Up to 2 controls (n = 342) were selected from the cohort for each case and matched by age, sex, race, and date of blood draw. MAIN OUTCOME MEASURE: Odds ratio (OR) of incident colon and rectal cancer. RESULTS: Plasma CRP concentrations were higher among all colorectal cases combined than controls (median CRP, 2.44 vs 1.94 mg/L; P =.01). The highest concentration was found in persons who subsequently developed colon cancer vs matched controls (median CRP, 2.69 vs 1.97 mg/L; P<.001). Among rectal cancer cases, CRP concentrations were not significantly different from controls (median CRP, 1.79 vs 1.81 mg/L; P =.32). The risk of colon cancer was higher in persons in the highest vs lowest quartile of CRP (OR, 2.55; 95% confidence interval [CI], 1.34-4.88; P for trend =.002). In nonsmokers, the corresponding association was stronger (OR, 3.51; 95% CI, 1.64-7.51; P for trend<.001). A 1-SD increase in log CRP (1.02 mg/L) was associated with an increased risk of colon cancer after adjusting for potential confounders and excluding cases occurring within 2 years of baseline (OR, 1.35; 95% CI, 1.05-1.74) or excluding those with late-stage colon cancer at the time of diagnosis (OR, 1.38; 95% CI, 0.99-1.91). CONCLUSIONS: Plasma CRP concentrations are elevated among persons who subsequently develop colon cancer. These data support the hypothesis that inflammation is a risk factor for the development of colon cancer in average-risk individuals.

Adult↗

Cross-sectional relations of urinary sodium excretion to cardiac structure and hypertrophy. The Framingham Heart Study.

BACKGROUND: Increased sodium intake has been positively associated with high blood pressure (BP) and hypertensive target organ damage, but associations with cardiac structure in nonhypertensive individuals have yielded inconsistent results. We tested the hypothesis that sodium intake is associated with left ventricular (LV) mass and left ventricular hypertrophy (LVH), independent of BP, in the community. METHODS: We analyzed the cross-sectional relationships between urinary sodium excretion and LV measurements in a community-based sample of 2660 Framingham Offspring Study participants (mean age 58 years, 56% women and 44% men). Participants with known coronary artery disease, congestive heart failure, or renal failure as well as those using diuretics were excluded. Urinary sodium excretion was measured on a spot urine sample and was indexed to urinary creatinine. RESULTS: In sex-specific, multivariable linear regression models adjusting for covariates known to influence LV measurements, log urinary sodium was not associated with LV mass, wall thickness, end-diastolic dimensions, or left atrial size in either sex. Urinary sodium was not related to LVH defined as LV mass >/= sex-specific 80th percentile value. In analyses restricted to hypertensive individuals (n = 983, 470 women), urinary sodium was not associated with LV mass or LVH. CONCLUSIONS: In our large community-based sample, urinary sodium excretion was not related to LV mass, function, or hypertrophy.

Aged↗