Biomedical subjects

N Rifai

Publications and source records attributed to N Rifai.

At least 19 recordsLinked to original sources

PubMed2001

Ability of minor elevations of troponins I and T to predict benefit from an early invasive strategy in patients with unstable angina and non-ST elevation myocardial infarction: results from a randomized trial.

CONTEXT: Cardiac troponins I (cTnI) and T (cTnT) are useful for assessing prognosis in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). However, the use of cardiac troponins for predicting benefit of an invasive vs conservative strategy in this patient population is not clear. OBJECTIVE: To prospectively test whether an early invasive strategy provides greater benefit than a conservative strategy in acute coronary syndrome patients with elevated baseline troponin levels. DESIGN: Prospective, randomized trial conducted from December 1997 to June 2000. SETTING: One hundred sixty-nine community and tertiary care hospitals in 9 countries. PARTICIPANTS: A total of 2220 patients with acute coronary syndrome were enrolled. Baseline troponin level data were available for analysis in 1821, and 1780 completed the 6-month follow-up. INTERVENTIONS: Patients were randomly assigned to receive (1) an early invasive strategy of coronary angiography between 4 and 48 hours after randomization and revascularization when feasible based on coronary anatomy (n = 1114) or (2) a conservative strategy of medical treatment and, if stable, predischarge exercise tolerance testing (n = 1106). Conservative strategy patients underwent coronary angiography and revascularization only if they manifested recurrent ischemia at rest or on provocative testing. MAIN OUTCOME MEASURE: Composite end point of death, MI, or rehospitalization for acute coronary syndrome at 6 months. RESULTS: Patients with a cTnI level of 0.1 ng/mL or more (n = 1087) experienced a significant reduction in the primary end point with the invasive vs conservative strategy (15.3% vs 25.0%; odds ratio [OR], 0.54; 95% confidence interval [CI], 0.40-0.73). Patients with cTnI levels of less than 0.1 ng/mL had no detectable benefit from early invasive management (16.0% vs 12.4%; OR, 1.4; 95% CI, 0.89-2.05; P<.001 for interaction). The benefit of invasive vs conservative management through 30 days was evident even among patients with low-level (0.1-0.4 ng/mL) cTnI elevation (4.4% vs 16.5%; OR, 0.24; 95% CI, 0.08-0.69). Directionally similar results were observed with cTnT. CONCLUSION: In patients with clinically documented acute coronary syndrome who are treated with glycoprotein IIb/IIIa inhibitors, even small elevations in cTnI and cTnT identify high-risk patients who derive a large clinical benefit from an early invasive strategy.

Adult↗

PubMed2001

Early noninvasive detection of failed epicardial reperfusion after fibrinolytic therapy.

Available noninvasive techniques for identifying patients with failed epicardial reperfusion after fibrinolytic therapy are limited by poor accuracy. It is unknown whether combining multiple noninvasive predictors would improve diagnostic accuracy and facilitate identification of candidates for rescue percutaneous coronary intervention. In the Thrombolysis In Myocardial Infarction (TIMI) 14 trial, we evaluated the ability of ST-segment resolution (n = 606), chest pain resolution (n = 859), and the ratio of 60-minute/baseline serum myoglobin (n = 308) to identify patients with angiographic evidence of failed reperfusion 90 minutes after fibrinolysis. Three criteria were prospectively defined: <50% ST resolution at 90 minutes, presence of chest pain at the time of angiography, and myoglobin ratio <4. Patients who met any individual criterion were more likely to have less than TIMI 3 flow and an occluded infarct-related artery (TIMI 0/1 flow) than those who did not meet the criterion (p <0.005 for each). When the 3 criteria were used together (n = 169), patients who satisfied 0 (n = 29), 1 (n = 68), 2 (n = 51), or 3 (n = 21) of the criteria had a 17%, 24%, 35%, and 76% probability of failing to achieve TIMI 3 flow (p <0.0001 for trend), a 0%, 6%, 18%, and 57% probability of an occluded infarct-related artery (p <0.0001 for trend), and a 0%, 1.5%, 2.0%, and 9.5% rate of 30-day mortality (p = 0.05 for trend), respectively. Use of the criteria in combination increased positive predictive values without decreasing negative predictive values. In conclusion, ST-segment resolution, chest pain resolution, and early washout of serum myoglobin can be used in combination to aid in the early noninvasive identification of candidates for rescue percutaneous coronary intervention.

Aged↗

PubMed2001

C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus.

CONTEXT: Inflammation is hypothesized to play a role in development of type 2 diabetes mellitus (DM); however, clinical data addressing this issue are limited. OBJECTIVE: To determine whether elevated levels of the inflammatory markers interleukin 6 (IL-6) and C-reactive protein (CRP) are associated with development of type 2 DM in healthy middle-aged women. DESIGN: Prospective, nested case-control study. SETTING: The Women's Health Study, an ongoing US primary prevention, randomized clinical trial initiated in 1992. PARTICIPANTS: From a nationwide cohort of 27 628 women free of diagnosed DM, cardiovascular disease, and cancer at baseline, 188 women who developed diagnosed DM over a 4-year follow-up period were defined as cases and matched by age and fasting status with 362 disease-free controls. MAIN OUTCOME MEASURES: Incidence of confirmed clinically diagnosed type 2 DM by baseline levels of IL-6 and CRP. RESULTS: Baseline levels of IL-6 (P<.001) and CRP (P<.001) were significantly higher among cases than among controls. The relative risks of future DM for women in the highest vs lowest quartile of these inflammatory markers were 7.5 for IL-6 (95% confidence interval [CI], 3.7-15.4) and 15.7 for CRP (95% CI, 6.5-37.9). Positive associations persisted after adjustment for body mass index, family history of diabetes, smoking, exercise, use of alcohol, and hormone replacement therapy; multivariate relative risks for the highest vs lowest quartiles were 2.3 for IL-6 (95% CI, 0.9-5.6; P for trend =.07) and 4.2 for CRP (95% CI, 1.5-12.0; P for trend =.001). Similar results were observed in analyses limited to women with a baseline hemoglobin A(1c) of 6.0% or less and after adjustment for fasting insulin level. CONCLUSIONS: Elevated levels of CRP and IL-6 predict the development of type 2 DM. These data support a possible role for inflammation in diabetogenesis.

Biomarkers↗

PubMed2001

Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study.

CONTEXT: Plasma levels of the inflammatory biomarker C-reactive protein (CRP) predict cardiovascular risk, and retrospective studies suggest that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) may lower CRP in a manner largely independent of low-density lipoprotein cholesterol (LDL-C). However, prospective trial data directly evaluating this anti-inflammatory effect of statins are not available. OBJECTIVE: To test the hypothesis that pravastatin has anti-inflammatory effects as evidenced by CRP reduction. DESIGN, SETTING, AND PARTICIPANTS: Community-based, prospective, randomized, double-blind trial including 1702 men and women with no prior history of cardiovascular disease (primary prevention cohort) and open-label study including 1182 patients with known cardiovascular disease (secondary prevention cohort) who provided at least baseline and 12-week blood samples. The study was conducted in US office-based practices from February to December 2000. INTERVENTIONS: Participants in the double-blind primary prevention trial were randomly assigned to receive 40 mg/d of pravastatin (n = 865) or placebo (n = 837) for 24 weeks. Participants in the secondary prevention cohort received 40 mg/d of open-label pravastatin for 24 weeks. MAIN OUTCOME MEASURE: Change in CRP levels from baseline to 24 weeks. RESULTS: In the primary prevention trial, compared with placebo, pravastatin reduced median CRP levels by 16.9% (P<.001) at 24 weeks, reflecting a decrease of 0.02 mg/dL in the pravastatin group while no change in CRP levels was observed in the placebo group. This effect was seen as early as 12 weeks (median reduction in CRP with pravastatin, 14.7%; P<.001) and was present among all prespecified subgroups according to sex, age, smoking status, body mass index, baseline lipid levels, presence of diabetes, and use of aspirin or hormone replacement therapy. No significant association was observed between baseline CRP and baseline LDL-C levels, end-of-study CRP and end-of-study LDL-C levels, or change in CRP and change in LDL-C levels over time. In linear regression analyses, the only significant predictors of change in CRP on a log scale were randomized pravastatin allocation and baseline CRP levels (P<.001 for both). Similar reductions in CRP levels were observed at 12 weeks (-14.3%) and 24 weeks (-13.1%) in the secondary prevention cohort treated with pravastatin (P<.005 for both). CONCLUSIONS: In this prospective trial, pravastatin reduced CRP levels at both 12 and 24 weeks in a largely LDL-C-independent manner. These data provide evidence that statins may have anti-inflammatory effects in addition to lipid-lowering effects.

Adult↗

PubMed2001

Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.

BACKGROUND: Elevated levels of C-reactive protein, even in the absence of hyperlipidemia, are associated with an increased risk of coronary events. Statin therapy reduces the level of C-reactive protein independently of its effect on lipid levels. We hypothesized that statins might prevent coronary events in persons with elevated C-reactive protein levels who did not have overt hyperlipidemia. METHODS: The level of C-reactive protein was measured at base line and after one year in 5742 participants in a five-year randomized trial of lovastatin for the primary prevention of acute coronary events. RESULTS: The rates of coronary events increased significantly with increases in the base-line levels of C-reactive protein. Lovastatin therapy reduced the C-reactive protein level by 14.8 percent (P<0.001), an effect not explained by lovastatin-induced changes in the lipid profile. As expected, lovastatin was effective in preventing coronary events in participants whose base-line ratio of total cholesterol to high-density lipoprotein (HDL) cholesterol was higher than the median ratio, regardless of the level of C-reactive protein (number needed to treat for five years to prevent 1 event, 47; P=0.005). However, lovastatin was also effective among those with a ratio of total to HDL cholesterol that was lower than the median and a C-reactive protein level higher than the median (number needed to treat, 43; P=0.02). In contrast, lovastatin was ineffective among participants with a ratio of total to HDL cholesterol and a C-reactive protein level that were both lower than the median (number needed to treat, 983; P=0.80). CONCLUSIONS: Statin therapy may be effective in the primary prevention of coronary events among subjects with relatively low lipid levels but with elevated levels of C-reactive protein.

Acute Disease↗

PubMed2001

Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.

CONTEXT: Several novel risk factors for atherosclerosis have recently been proposed, but few comparative data exist to guide clinical use of these emerging biomarkers. OBJECTIVE: To compare the predictive value of 11 lipid and nonlipid biomarkers as risk factors for development of symptomatic peripheral arterial disease (PAD). DESIGN, SETTING, AND PARTICIPANTS: Nested case-control study using plasma samples collected at baseline from a prospective cohort of 14 916 initially healthy US male physicians aged 40 to 84 years, of whom 140 subsequently developed symptomatic PAD (cases); 140 age- and smoking status-matched men who remained free of vascular disease during an average 9-year follow-up period were randomly selected as controls. MAIN OUTCOME MEASURE: Incident PAD, as determined by baseline total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol-HDL-C ratio, triglycerides, homocysteine, C-reactive protein (CRP), lipoprotein(a), fibrinogen, and apolipoproteins (apo) A-I and B-100. RESULTS: In univariate analyses, plasma levels of total cholesterol (P<.001), LDL-C (P =.001), triglycerides (P =.001), apo B-100 (P =.001), fibrinogen (P =.02), CRP (P =.006), and the total cholesterol-HDL-C ratio (P<.001) were all significantly higher at baseline among men who subsequently developed PAD compared with those who did not, while levels of HDL-C (P =.009) and apo A-I (P =.05) were lower. Nonsignificant baseline elevations of lipoprotein(a) (P =.40) and homocysteine (P =.90) were observed. In multivariable analyses, the total cholesterol-HDL-C ratio was the strongest lipid predictor of risk (relative risk [RR] for those in the highest vs lowest quartile, 3.9; 95% confidence interval [CI], 1.7-8.6), while CRP was the strongest nonlipid predictor (RR for the highest vs lowest quartile, 2.8; 95% CI, 1.3-5.9). In assessing joint effects, addition of CRP to standard lipid screening significantly improved risk prediction models based on lipid screening alone (P<.001). CONCLUSIONS: Of 11 atherothrombotic biomarkers assessed at baseline, the total cholesterol-HDL-C ratio and CRP were the strongest independent predictors of development of peripheral arterial disease. C-reactive protein provided additive prognostic information over standard lipid measures.

Adult↗

PubMed2001

Rapid reduction in C-reactive protein with cerivastatin among 785 patients with primary hypercholesterolemia.

BACKGROUND: Long-term therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) has been shown to reduce levels of C-reactive protein (CRP). However, the generalizability, speed of onset, and dose-response characteristics of this effect are uncertain. METHODS AND RESULTS: We measured CRP, LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) levels among 785 patients with primary hypercholesterolemia at baseline and after 8 weeks of therapy with either 0.4 or 0.8 mg of cerivastatin. Overall, cerivastatin resulted in a 13.3% reduction in median CRP levels (P:<0.001) and a 24.5% reduction in mean CRP levels (P:<0.001). Although LDL-C promptly decreased in a dose-dependent manner (mean LDL-C reduction, 37.3% for 0.4 mg and 42.2% for 0.8 mg of cerivastatin), no clear dose-response effect of cerivastatin on CRP was observed, nor was there any substantive correlation between the magnitude of change in CRP and the magnitude of change in LDL-C (r=-0.08) or the magnitude of change in HDL-C (r=-0.04). Thus, <2% of the variance in the percent change in CRP over 8 weeks could be attributed to the percent change in either of these lipid parameters. Further, there was no evidence of correlation between baseline CRP levels and baseline lipid levels or between end-of-study CRP levels and end-of-study lipid levels. CONCLUSIONS: Among 785 patients with primary hypercholesterolemia, CRP levels were significantly reduced within 8 weeks of initiating cerivastatin therapy in a lipid-independent manner.

Administration, Oral↗

PubMed2001

Soluble P-selectin and the risk of future cardiovascular events.

BACKGROUND: P-selectin, a cell-surface adhesion molecule involved in leukocyte rolling and attachment, has been hypothesized to play a role in the initiation of atherosclerosis. However, little clinical data are available evaluating the role of soluble P-selectin in determining vascular risk. METHODS AND RESULTS: In a large-scale prospective study of apparently healthy women, we measured baseline plasma concentration of soluble P-selectin among 115 participants who subsequently developed cardiovascular events and among 230 age- and smoking-matched participants who remained free of disease during 3.5 years of follow-up. Overall, mean levels of soluble P-selectin were significantly higher at baseline among women who subsequently experienced cardiovascular events compared with those who did not (83.2 versus 69.3 ng/mL; P:=0.003). The risk of future cardiovascular events increased with increasing quartiles of soluble P-selectin (P:=0.02), such that women in the highest quartile at study entry had an age- and smoking-matched relative risk 2.2 times higher than those in the lowest quartile (95% confidence interval, 1.2 to 4.2; P:=0.01). This effect was independent of traditional risk factors. For each quartile increase in soluble P-selectin, the risk of future cardiovascular events increased 28% (P:=0.03) after additional adjustment for obesity, hypertension, hyperlipidemia, diabetes, and exercise frequency. The highest risks were observed among women with the very highest levels of P-selectin (>137.3 ng/mL, the 95th percentile cut point of the control distribution). CONCLUSIONS: Soluble P-selectin levels are elevated among apparently healthy women at risk for future vascular events.

Age Factors↗

PubMed2001

The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity.

PURPOSE: To compare the protective effect of dexrazoxane (DRZ) against cardiotoxicity induced by doxorubicin (DXR) and mitoxantrone (MTX). METHODS: Adult male spontaneously hypertensive rats (SHR) were treated with 1 mg/kg DXR (i.v.) or 0.5 mg/kg MTX (i.v.), either alone or 30 min after 25 mg/kg DRZ (i.p.) weekly for up to 12 weeks. Animals treated with DXR alone either died (n = 2) or were killed (n = 3) at a cumulative dose of 10 mg/kg. The severity of cardiac lesions (cytoplasmic vacuolization and myofibrillar loss) were graded semiquantitatively by light microscopy on a scale of 0 to 3. RESULTS: Cardiac lesions were observed in all SHR given DXR or MTX alone, and were attenuated in those given DRZ prior to either DXR (mean lesion scores 2.7 vs 1.5; P < 0.05) or MTX (mean lesion scores 2.0 vs 1.25; P < 0.05). Cardioprotection was also demonstrated by monitoring serum levels of cardiac troponin T (cTnT), which were elevated in all animals receiving DXR or MTX alone. These elevations were attenuated in SHR given the combination of DXR and DRZ (mean values 0.79 ng/ml vs 0.24 ng/ml; P < 0.05) and MTX and DRZ (mean values 0.19 ng/ml vs 0.04 ng/ ml; P < 0.05). Biochemical studies have shown that both DXR and MTX form potentially cardiotoxic complexes with iron. ADR-925 (the hydrolysis product of DRZ) and other chelators (EDTA, diethylenetriaminepentaacetic acid and desferrioxamine) removed Fe(III) from its complex with MTX or DXR. CONCLUSIONS: The present study showed that DRZ significantly attenuates the cardiotoxicity induced by DXR and MTX, and that this protective activity can be assessed by morphological evaluation of cardiac tissues and by monitoring the concentrations of cTnT in serum.

Animals↗

PubMed2001

Gender differences in exercise-induced changes in sex hormone levels and lipid peroxidation in athletes participating in the Hawaii Ironman triathlon. Ginsburg-gender and exercise-induced lipid peroxidation.

BACKGROUND: Exercise reduces the risk of coronary heart disease in men and women but paradoxically, may promote free-radical formation, lipid peroxidation and vascular tissue injury. In this study, we assessed whether exercise-induced oxidative stress similarly affected men and women who participated in the Hawaii Ironman triathlon. METHODS AND RESULTS: Fifty-seven athletes (38 males) who completed the triathlon (3.9 km swim, 180.2 km bike, 42.2 km run) participated in this study. Blood samples were obtained 2 days before and immediately after the triathlon for the measurement of lipids, antioxidants and sex hormones and for the assessment of the susceptibility of plasma lipids to peroxidation. Lipid changes after exercise were similar for men and women. However, the susceptibility of plasma lipids to peroxidation was reduced by 61% (P < 0.001) in men and only 14% (P = NS) in women postrace. These changes were not associated with the supplemental use or levels of antioxidants. In addition, in men there was an increase of 58% in the antioxidant sex hormone estradiol and a decrease of 58% in testosterone (P < 0.001) postrace. No significant changes were noted for these two hormones in women. CONCLUSIONS: There are significant gender-specific differences in the susceptibility of lipids to peroxidation and in changes in estradiol and testosterone levels as a result of ultra-endurance exercise. These changes may in part explain the salutary effect of exercise on the development of vascular disease.

Adult↗

PubMed2001

Performance characteristics of a point of care C-reactive protein assay.

BACKGROUND: C-reactive protein (CRP) is a non-specific marker of inflammation that can be used for atherosclerotic risk assessment. This application requires increased precision at low CRP concentrations compared to traditional assays. METHODS: The Micros CRP analyzer (ABX Diagnostics) is a small bench top device. Its limit of detection, limit of quantitation, linearity and imprecision were assessed. Method comparison studies were performed using samples both inside and outside the reference interval. Anticoagulant effects and the prozone effect were also evaluated. RESULTS: The limit of detection was 0.1 mg/l. The method was linear from 2 to 60 and 0.3 to 60 mg/l using systematic error limits of 10% and 20%, respectively. The total imprecision was <8% for CRP concentrations from 0.7 to 9.1 mg/l. A prozone effect was seen at CRP concentrations >500 mg/l. Using samples from 120 apparently healthy adults, the Micros CRP method demonstrated excellent concordance with the BN II high sensitivity CRP (hs-CRP) method. The Micros CRP method compared well with a nephelometric method using samples with elevated CRP concentrations. CONCLUSIONS: The Micros CRP method is adequate for atherosclerotic risk prediction in clinical practice but does not have adequate accuracy at CRP concentrations <2 mg/l for epidemiological studies.

Adult↗

PubMed2001

Plasma insulin, leptin, and soluble TNF receptors levels in relation to obesity-related atherogenic and thrombogenic cardiovascular disease risk factors among men.

Obesity is related to cardiovascular disease (CVD) morbidity and mortality, however, the mechanisms for the development of obesity-induced CVD risk remain unclear. Hyperinsulinemia and insulin resistance are considered key components in the metabolic cardiovascular syndrome and as independent risk factors for CVD. Plasma leptin and tumor necrosis factor-alpha (TNF-alpha), two adipocyte products, are also proposed to be associated with the development of CVD risk. The purpose of this study is to evaluate the association of plasma leptin, soluble TNF receptors (sTNF-R), and insulin levels as possible mediators of the effect of obesity on atherogenic and thrombogenic CVD risk factors among men. From the Health Professionals Follow-up Study (HPFS), we selected 268 men, aged 47--83 years, who were free of CVD, diabetes, and cancer (except non-melanoma skin cancer), and who had provided a fasting blood sample in 1994. We measured plasma insulin and leptin levels by radioimmunoassay and sTNF-R levels by ELISA. Men in the highest quintile of body mass index (BMI, mean=30.5 kg/m(2)) were less physically active and had a more adverse cardiovascular lipid and homeostatic profile, as indicated by levels of insulin, triglyceride (TG), tissue plasminogen activator (t-PA) antigen levels, and apolipoprotein A1 (Apo-A1). In a multivariate regression model controlling for age, smoking, alcohol intake, physical activity and diet, BMI was inversely associated with HDL-cholesterol (HDL-C) and Apo-A1 and positively associated with TG, Apo-B and t-PA antigen levels. The associations between BMI and these CVD risk factors were only slightly changed after adjusting for leptin and/or sTNF-R; but were substantially attenuated after controlling for insulin levels. These data suggest that the association between obesity and biological predictors of CVD may be mediated through changes in plasma insulin, rather than leptin or sTNF-R levels. However, plasma leptin may still play a role in CVD through independent effects on lipid metabolism.

Adult↗

PubMed2001

Dietary and lifestyle factors in relation to plasma leptin concentrations among normal weight and overweight men.

OBJECTIVE: Leptin, the product of the obesity (ob) gene, is a multi-functional polypeptide that is important in energy metabolism, which is strongly correlated with body fat mass and body mass index (BMI). In a recent prospective study, we found that leptin was positively associated with 4 y weight gain among overweight and obese men. This suggests that leptin resistance, marked by hyperleptinemia among obese subjects, may be an important marker for weight gain. The purpose of this study is to evaluate whether modifiable dietary and lifestyle factors are associated with plasma leptin concentrations among US men. METHODS: We included 268 men aged 47--83 y (who were free of cardiovascular disease, diabetes mellitus and cancer, except nonmelanoma skin cancer) from the ongoing Health Professionals Follow-up Study. These subjects completed a detailed dietary and lifestyle questionnaire (including cigarette smoking, alcohol drinking and physical activity) and provided a fasting venous blood sample in 1994. All blood samples were stored in a deep freeze (-70 degrees C) for 4--5 y before being analyzed. Plasma leptin concentrations were measured by radioimmunoassay. RESULTS: Men in the highest quintile of plasma leptin (mean=14.4 ng/ml) weighed more, were less physically active, and had higher total and saturated fat and cholesterol intake than men in the lowest quintile (mean=3.0 ng/ml). Physical activity and current smoking were inversely associated with plasma leptin concentrations (P<0.001). A 20 MET difference in physical activity per week (equivalent to approximately 3 h of jogging) was associated with 0.38--0.58 ng/ml lower plasma leptin concentrations for normal weight and overweight men after adjusting for total energy and fat intake, BMI and other confounding variables. Total fat and monounsaturated fat intakes were positively associated with plasma leptin concentrations even after adjusting for BMI and other confounding variables; however, this association was limited to men of normal weight (BMI<25 kg/m(2)). CONCLUSION: These data suggest that physical activity may be a significant determinant of plasma leptin concentrations in men. Increasing physical activity is associated with lower plasma leptin concentrations even after adjusting for BMI. Physical activity may lower leptin concentrations not only due to decreased body fat mass, but potentially through an increase in leptin sensitivity. International Journal of Obesity (2001) 25, 106-114

Aged↗

PubMed2001

Plasma leptin concentrations and four-year weight gain among US men.

OBJECTIVE: Leptin, a primarily adipose tissue-derived protein product of the obesity (ob) gene, is an important regulator of energy metabolism. The strong association between body fat mass and elevated circulating leptin levels in humans suggests that leptin resistance, rather than leptin production, may contribute to the development of obesity and associated disorders. The purpose of this study is to evaluate the relationship between circulating plasma leptin levels and regulation of body weight over time among US men. DESIGN: Four-year prospective study. SUBJECTS: A total of 247 men from the Health Professionals Follow-up Study, who at baseline (1994), were 47-64 y of age, were free of cardiovascular diseases, diabetes mellitus and malignant neoplasmas, and completed a detailed lifestyle questionnaire. In addition, all participants completed a follow-up questionnaire in 1998. MEASUREMENTS: Baseline plasma leptin levels and 4-y weight change. RESULTS: At the start of follow-up, men in the highest quintile for plasma leptin (mean=12.1 ng/ml) weighed more, were less physically active, and had higher circulating insulin levels than men in the lowest quintile (mean=2.7 ng/ml). After adjustments for baseline age, weight, height, smoking status, alcohol intake, and physical activity, each 10 ng/ml increase in plasma leptin concentration was associated with a 1.68 kg (95% CI 0.14-3.18 kg) weight gain over the 4-y follow-up period. The observed association between leptin level and weight gain was limited to men with a baseline body mass index (BMI) of > or =25 kg/m2, in whom a 10 ng/ml higher baseline leptin was associated with a 2.45 kg (95% CI 0.73-4.18-kg) weight gain. Further adjustments for baseline total energy intake, plasma insulin and soluble tumor necrosis factor receptors levels did not appreciably alter these results. Plasma insulin level was not independently associated with subsequent weight gain. CONCLUSION: These results suggest that elevated plasma leptin concentrations among overweight men may be a marker of leptin resistance and subsequent weight gain.

Anthropometry↗

PubMed2001

Association between dietary patterns and plasma biomarkers of obesity and cardiovascular disease risk.

BACKGROUND: Although the effects of individual foods or nutrients on the development of diseases and their risk factors have been investigated in many studies, little attention has been given to the effect of overall dietary patterns. OBJECTIVE: Our objective was to examine the associations of 2 major dietary patterns, Western and prudent, with biomarkers of obesity and cardiovascular disease (CVD) risk. DESIGN: We used factor analysis to define major dietary patterns for a subsample of men (n = 466) from the Health Professionals Follow-up Study by using dietary information collected from food-frequency questionnaires (FFQs) in 1994. We calculated partial correlation coefficients between pattern scores and biomarker values adjusted for age, smoking status, energy and alcohol intake, physical activity, hours of television watching, and body mass index. RESULTS: We derived 2 major dietary patterns that were generally reproducible over time. The first pattern (prudent) was characterized by higher intakes of fruit, vegetables, whole grains, and poultry. The second pattern (Western) was characterized by higher intakes of red meats, high-fat dairy products, and refined grains. Using pattern scores from 1994 and adjusting for potential confounders, we found significant positive correlations between the Western pattern and insulin, C-peptide, leptin, and homocysteine concentrations, and an inverse correlation with plasma folate concentrations. The prudent pattern was positively correlated with plasma folate and inversely correlated with insulin and homocysteine concentrations. CONCLUSION: Major dietary patterns are predictors of plasma biomarkers of CVD and obesity risk, suggesting that the effect of overall diet on CVD risk may be mediated through these biomarkers.

Adult↗

PubMed2001

The pharmacokinetics of epidural ropivacaine in infants and young children.

UNLABELLED: The pharmacokinetic variables of ropivacaine were characterized after epidural bolus injection in pediatric patients. The subjects, 7 infants (aged 3-11 mo) and 11 young children (aged 12-48 mo), received 1.7 mg/kg of ropivacaine via a lumbar epidural catheter. Total plasma concentrations of ropivacaine measured over 24 h were assayed by high-pressure liquid chromatography, and pharmacokinetic modeling was performed by Nonlinear Mixed Effects Modeling analysis. The median peak venous plasma concentrations (C(max)) in infants and young children were 610 microg/L (interquartile range [IQR], 550-725 microg/L) and 640 microg/L (IQR, 540-750 microg/L), respectively. The median times to maximum plasma ropivacaine concentration (T(max)) were 60 min (IQR, 60-120 min) in infants and 60 min (IQR, 30-90 min) in young children. There were no statistical differences between median values of C(max) and T(max) between infants and young children. The calculated clearance (CL) in infants was 4.26 mL x min(-1) x kg(-1) (9% coefficient of variation), and in young children it was 6.15 mL x min(-1) x kg(-1) (11% coefficient of variation). The CL for infants was significantly less than the CL for young children (P < 0.01). The volume of distribution was estimated to be 2370 mL/kg (9% coefficient of variation) for both young children and infants. No systemic toxicity was observed in either group. IMPLICATIONS: This study revealed that the pharmacokinetic variables of lumbar epidural bolus ropivacaine in pediatric patients aged 3 to 48 mo are similar to those of adults, except that drug clearance was less in infants compared with older children.

Algorithms↗

PubMed2001

Simultaneous measurement of plasma ropivacaine and bupivacaine concentrations by HPLC with UV detection.

The authors developed a high-performance liquid chromatography (HPLC) assay for the simultaneous determination of plasma ropivacaine and bupivacaine concentrations using ultraviolet (UV) detection and a simple solid-phase extraction procedure. The absolute retention times of ropivacaine, bupivacaine, and the internal standard pentycaine were 1.9, 3.0, and 5.6 minutes, respectively. The assay had a linearity of 2000 ng/mL, a sensitivity of 5 ng/mL, an average recovery of 98%, and an average day-to-day imprecision of <10% for both drugs. A patient correlation study (n = 23) using this HPLC method and an established gas chromatographic assay revealed a slope of 1.01, an intercept of -10.6 ng/mL, and a correlation coefficient of 0.99 for ropivacaine; and a slope of 0.96, an intercept of 14.7 ng/mL, and a correlation coefficient of 0.99 for bupivacaine. Of the 60 different drugs tested, only quinidine and lidocaine extracted but did not interfere with the measurement of the drugs of interest. The authors conclude that the method described here is ideally suited for the therapeutic monitoring of plasma ropivacaine and bupivacaine concentrations.

Amides↗

PubMed2001

Blood pressure and inflammation in apparently healthy men.

Inflammation plays an important role in the development of atherosclerosis, but the specific stimuli governing cytokine release in atherogenesis are unknown. We examined the hypothesis that hypertension may increase the risk of atherosclerosis via proinflammatory effects. In a cross-sectional study involving 508 apparently healthy men, we studied the association between blood pressure and baseline plasma concentrations of 2 inflammatory markers, intercellular adhesion molecule-1 (sICAM-1) and interleukin-6 (IL-6). Increase in systolic blood pressure (SBP) (P=0.003), pulse pressure (PP) (P=0.019), and mean arterial pressure (P=0.014) was significantly associated with levels of sICAM-1. All of these measures of blood pressure, as well as diastolic blood pressure (DBP), were significantly associated with levels of IL-6 (all, P</=0.001). In multiple linear regression models controlled for age and other cardiac risk factors, SBP (7.6 ng/mL per 10 mm Hg, P=0.016) and PP (8.13 ng/mL per 10 mm Hg, P=0.038) were significantly associated with sICAM-1 levels, whereas SBP (0.11 pg/mL per 10 mm Hg, P<0.001), DBP (0.11 pg/mL per 10 mm Hg, P=0.008), PP (0.10 pg/mL per 10 mm Hg, P=0.009), and mean arterial pressure (0.15 pg/mL per 10 mm Hg, P<0.001) had similar strong relationships with log-transformed IL-6 levels. Therefore, in apparently healthy men, we observed significant graded relationships between blood pressure and levels of sICAM-1 as well as IL-6. These data suggest that increased blood pressure may be a stimulus for inflammation and that this is a possible mechanism underlying the well-established role of hypertension as a risk factor for atherosclerotic disease.

Blood Pressure↗