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ABSTRACT: Rheumatoid arthritis (RA) is associated with enhanced cardiovascular (CV) risk and subclinical vascular disease. The proinflammatory milieu has been linked to premature atherosclerosis and endothelial dysfunction in RA. While interleukin 17 (IL-17) is considered pathogenic in RA, its role in determining vascular dysfunction in this disease has not been systematically assessed.
To analyse candidate variables that might determine endothelial function in various vascular territories in a cohort of patients with RA receiving treatment with biological agents, with minimal traditional CV risk factors and low disease activity score.
Patients with RA (n=50) receiving stable treatment with biological agents underwent measurement of conduit artery endothelial function by brachial artery flow-mediated dilatation; arterial compliance by pulse wave velocity (PWV) assessment; and endothelium-dependent microvascular testing with Endo-Pat2000 device to assess the reactive hyperaemia index (RHI). IL-17 was quantified by ELISA and disease activity was assessed by 28-joint count Disease Activity Score.
IL-17 was the main determinant of lower RHI in univariate and multivariate analysis. Traditional and non-traditional CV risk variables determined PWV, with a significant positive association with IL-17 in univariate and multivariate analysis. In contrast, conduit endothelial function was mainly determined by rheumatoid factor titres in univariate and multivariate analysis. Anti-cyclic citrullinated peptide titres, specific disease-modifying antirheumatic drugs or biological agents and disease activity did not determine vascular function.
In patients with RA treated with biological agents, IL-17 is a main predictor of microvascular function and arterial compliance. This study suggests that IL-17 may play a significant role in development of endothelial dysfunction and cardiovascular disease in RA.
Annals of the rheumatic diseases 09/2011; 70(9):1550-5. · 8.11 Impact Factor
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The American journal of medicine 06/2011; 124(8):705-7. · 4.47 Impact Factor
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ABSTRACT: Studies have demonstrated an influence of dosage release formulations on drug interactions and enantiomeric plasma concentrations. Metoprolol is a commonly used beta-adrenergic antagonist metabolized by CYP2D6. The CYP2D6 inhibitor paroxetine has previously been shown to interact with metoprolol tartrate. This open-label, randomized, 4-phase crossover study assessed the potential differential effects of paroxetine on stereoselective pharmacokinetics of immediate-release (IR) tartrate and extended-release (ER) succinate metoprolol formulations. Ten healthy participants received metoprolol IR (50 mg) and ER (100 mg) with and without paroxetine coadministration. Blood samples were collected over 24 hours for determination of metoprolol plasma enantiomer concentrations. Paroxetine coadministration significantly increased S and R metoprolol area under the plasma concentration-time curve from time 0 to the 24-hour blood draw (AUC(0-24h)) by 4- and 5-fold, respectively for IR, and 3- and 4-fold, respectively, for ER. S/R AUC ratios significantly decreased. These results demonstrate a pharmacokinetic interaction between paroxetine and both formulations of metoprolol. The interaction is greater with R metoprolol, and stereoselective metabolism is lost. This could theoretically result in greater beta-blockade and lost cardioselectivity. The magnitude of the interaction was similar between metoprolol formulations, which may be attributable to low doses/drug input rates employed.
The Journal of Clinical Pharmacology 03/2011; 51(3):389-96. · 2.91 Impact Factor
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ABSTRACT: to assess the impact of paroxetine coadministration on the stereoselective pharmacokinetic (PK) properties of carvedilol.
prospective, randomized, 2-phase crossover.
the University of Michigan General Clinical Research Unit and Michigan Clinical Research Unit.
twelve healthy volunteers aged 18 to 45 years, male and female, receiving no treatment with prescription or nonprescription medications.
participants received single dose oral carvedilol (12.5 mg) with and without coadministration of immediate-release paroxetine (10 mg orally twice daily), in random order. Blood samples were collected at 0, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 10, 12, and 24 hours post-carvedilol dose for determination of R and S carvedilol plasma enantiomer concentrations by high pressure liquid chromatography.
pharmacokinetic (PK) parameters were calculated for each enantiomer by noncompartmental methods and compared between study phases by analysis of variance (ANOVA) controlling for study phase order and subject, with Tukey's studentized range test post hoc. Area under the concentration-time curve (AUC) increased significantly with paroxetine coadministration, approximately 2.5-fold and 1.9-fold for the R and S enantiomers, respectively. R/S AUC ratio increased significantly, from approximately 2.3 to 3.0. Individual increases in enantiomeric AUCs with paroxetine coadministration ranged from 0% to 571% and changes in R/S ratio ranged from -8% to 108%. Heart rate, P-R interval, and blood pressure were monitored and no clinically significant changes in carvedilol effects were noted.
this study demonstrated a PK drug-drug interaction between paroxetine and carvedilol, with considerable interparticipant variability in carvedilol PK parameters and magnitude of drug interaction. Stereoselectivity of carvedilol metabolism is preserved with paroxetine coadministration, and R/S AUC ratio generally widens. Although this drug interaction could potentially increase adrenergic antagonism and have significant clinical effects in patients, these effects were not seen in our healthy volunteer participants.
Journal of Cardiovascular Pharmacology and Therapeutics 12/2010; 15(4):373-9. · 1.75 Impact Factor
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ABSTRACT: Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16alpha-hydroxyoestrone (16alpha-OHE1) are thought to curtail the greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related oestrogen levels to F(2a)-isoprostane levels, a biomarker of oxidative stress.
Data were obtained from 1647 women, aged 47-57 years, participating in the fifth annual follow-up of the Study of Women's Health Across the Nation (SWAN), a study of the menopausal transition.
Serum E2 and urinary 2-OHE1 and 16alpha-OHE1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and urinary F(2a)-isoprostanes were measured by enzyme immunoassay (EIA).
F(2a)-isoprostane concentrations were elevated in women who smoked, a behaviour associated with increased oxidative stress, but not in stages of the natural menopause. Mean F(2a)-isoprostane concentrations among pre- and postmenopausal women who smoked were 1082 and 1064 pg/ml, respectively, values double those in pre- (343 pg/ml) and postmenopausal (379 pg/ml) nonsmoking women. 2-OHE1 and F(2a)-isoprostane concentrations were positively and highly correlated (partial correlations rho(Y|X) = 0.44 and rho(Y|X) = 0.43 in pre- and postmenopausal women, respectively). Similarly, 16alpha-OHE1 concentrations were positively and highly correlated with F(2a)-isoprostane concentrations (rho(Y|X) = 0.52 and rho(Y|X) = 0.59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F(2a)-isoprostanes only in postmenopausal women (rho(Y|X) = 0.20). Associations were adjusted for age, body mass index (BMI), race/ethnicity, lipids, physical activity level and alcohol consumption.
This study does not support the commonly held hypothesis that levels of endogenous E2 or its oestrone metabolites favourably modify oxidative stress by decreasing F2(a)-isoprostane levels.
Clinical Endocrinology 06/2008; 68(5):806-13. · 3.17 Impact Factor
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ABSTRACT: To determine how often primary care physicians discuss medication costs with their senior patients and what cost-reducing strategies they employ.
Cross-sectional, random-sample mail questionnaire.
State of California.
Six hundred seventy-eight of 1,098 (62%) internal medicine and family practice physicians selected from the American Medical Association Masterfile.
Main outcomes included frequency of cost discussions with senior patients in the previous 30 days and choice of cost-reducing strategy when a senior expresses financial difficulty with medication costs.
Forty-three percent of physicians reported discussing medication cost with at least half of their senior patients in the previous 30 days. Patients initiated most of these discussions. Forty percent reported that, at least one time in the previous 30 days, they had not discussed cost but wished they had. The most common reason given was "I ran out of time" (36%). Physicians with high perceived knowledge of medication costs were more likely to discuss cost (odds ratio (OR)=3.49, 95% confidence interval (CI)=1.66-7.3) versus low perceived knowledge, but this trend was not seen in physicians who scored high on actual knowledge of medication costs (OR=0.78, 95% CI=0.43-1.43) versus low actual knowledge. The most common cost-reducing strategies were generic substitution (33%) and offering samples (25%).
The frequency of medication cost discussions between physicians and senior patients is low, and when it occurs, is often initiated by patients. Physicians' perception of their knowledge of medication costs may be an important factor in initiating cost discussions.
Journal of the American Geriatrics Society 02/2007; 55(1):102-7. · 3.74 Impact Factor
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ABSTRACT: The renin-angiotensin system (RAS) may play a role in vascular aging. The authors hypothesized that blockade of the angiotensin II type 1 receptor with an angiotensin receptor blocker in healthy elderly subjects improves vascular compliance and endothelial function. Thirty-five healthy elderly subjects were randomized to valsartan or placebo in a double-blind crossover study after baseline testing for pulse wave velocity, aortic augmentation index, and brachial artery flow-mediated dilation. Angiotensin II type 1 receptor blockade with valsartan improved vascular compliance but not flow-mediated dilation. Changes in pulse wave velocity with valsartan were correlated with change in central systolic blood pressure and pulse pressure and remained associated on multivariate analysis. Change in pulse wave velocity after adjusting for degree of blood pressure change, age, and sex remained correlated with assignment to the angiotensin receptor blocker but not placebo. These data suggest that angiotensin II type 1 receptor blockade improves aging-related vascular compliance without alterations in flow-mediated dilation. Mechanisms regulating compliance and endothelial function are complex and may not necessarily converge in aging.
Journal of Clinical Hypertension 12/2006; 8(11):783-90. · 1.83 Impact Factor
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ABSTRACT: The renin-angiotensin system (RAS) may play a role in vascular aging. The authors hypothesized that blockade of the angiotensin II type 1 receptor with an angiotensin receptor blocker in healthy elderly subjects improves vascular compliance and endothelial function. Thirty-five healthy elderly subjects were randomized to valsartan or placebo in a double-blind crossover study after baseline testing for pulse wave velocity, aortic augmentation index, and brachial artery flow-mediated dilation. Angiotensin II type 1 receptor blockade with valsartan improved vascular compliance but not flowmediated dilation. Changes in pulse wave velocity with valsartan were correlated with change in central systolic blood pressure and pulse pressure and remained associated on multivariate analysis. Change in pulse wave velocity after adjusting for degree of blood pressure change, age, and sex remained correlated with assignment to the angiotensin receptor blocker but not placebo. These data suggest that angiotensin II type 1 receptor blockade improves aging-related vascular compliance without alterations in flow-mediated dilation. Mechanisms regulating compliance and endothelial function are complex and may not necessarily converge in aging.
Journal of Clinical Hypertension 10/2006; 8(11):783 - 790. · 1.83 Impact Factor
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ABSTRACT: Flow-mediated dilation (FMD) in the brachial artery is a widely used end point in clinical trials despite large within-subject variability and a small dynamic range. Recent studies suggest that the radial artery may be more advantageous for investigating FMD because of an enhanced vasodilator response. This study therefore assessed the validity and repeatability of radial artery FMD (FMD-R) to evaluate its suitability for the noninvasive evaluation of endothelial function. Thirty-three healthy subjects were recruited over a period of 11 months. Intra- and inter-reader reproducibilities were measured with high-resolution ultrasound at 4 time points: twice 1 morning (1 to 3 hours apart) and twice again within 7 days (range 4 to 9 days between visits). Conduit endothelial-dependent and -independent vasomotion were assessed by responses to reactive hyperemia and nitroglycerin, respectively. FMD-R measurements demonstrated significant intra- and interday variabilities (intraclass correlation coefficients [ICCs] 0.38 and 0.23, p = 0.04 and 0.12, respectively). Bland-Altman plots confirmed the test-retest variation in FMD-R. In contrast, radial artery diameter measurements (intra- and inter-reader) demonstrated a high degree of repeatability (interstudy ICC >0.8, p <0.0001). The number of subjects needed to detect a treatment difference of 2% in FMD-R with a p value of 0.05 and a power of 0.80 would be 118 in a crossover design and 234 in a parallel design for assessing group changes. In conclusion, these findings show that FMD-R is highly variable within subjects, even in a healthy population, after adjusting for multiple technical factors and implies biologic variation in radial artery tone.
The American Journal of Cardiology 12/2005; 96(9):1345-8. · 3.37 Impact Factor
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ABSTRACT: Raynaud's syndrome (RS), which is characterized by recurrent episodes of vasospasm with exposure to cold, may occur alone (primary RS) or in association with connective tissue diseases or other underlying conditions (secondary RS). We investigated the effect of cilostazol on vessel wall responses in RS. Patients were diagnosed (primary or secondary RS associated with connective tissue diseases) and randomized to placebo or cilostazol 100 mg twice daily for 6 weeks in a double-blind manner. Brachial artery vasoreactivity, laser Doppler fluxmetry, and cold pressor testing (CPT) were performed at study initiation and completion. Symptoms were assessed using standardized questionnaires. Forty subjects completed the study (19 with primary RS and 21 with secondary RS). Cilostazol significantly increased the mean brachial artery diameter at 6 weeks (primary RS, p = 0.006; secondary RS, p = 0.06). There was no change in median flow-mediated dilation (FMD) with cilostazol in primary RS (25th, 75th percentiles) (4.06% [2.5, 6.1] to -0.77% [-2.4, 3.4] or secondary RS (2.2% [0.05, 6.3] to 2.95% [1.7, 7.4]). There were no changes in nitroglycerin-mediated dilation or microvascular flow indexes in either cohort. In patients with primary RS, cilostazol treatment yielded a positive change in the slope of brachial responsiveness to CPT (increase of 0.32 mm/min; p = 0.002 vs placebo). Cilostazol treatment remained significantly associated with increased brachial artery diameter when controlling for baseline values (p = 0.018). Cilostazol increased conduit vessel diameter in patients with primary and secondary RS, with a favorable impact on conduit vessel responsiveness to cold in patients with primary RS without affecting microvascular flow or symptoms.
The American Journal of Cardiology 01/2004; 92(11):1310-5. · 3.37 Impact Factor
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ABSTRACT: To compare microvascular and macrovascular functions in a cohort of patients with primary and secondary Raynaud's phenomenon (RP) who were matched for demographic, risk factor, and severity profiles.
Forty patients with primary or secondary RP matched for vascular risk factors and severity scores underwent testing of endothelial function and cold pressor responsiveness of the brachial artery. Microvascular perfusion of the digital vasculature was assessed using laser Doppler fluxmetry in response to reactive hyperemia. Plasma was assayed for endothelin 1 (ET-1), asymmetric dimethylarginine (ADMA), intercellular adhesion molecule 1, vascular cell adhesion molecule 1 (VCAM-1), and monocyte chemoattractant protein 1 (MCP-1).
Patients with RP had abnormal vasoconstrictor responses to cold pressor tests (CPT) that were similar in primary and secondary RP. There were no differences in median flow-mediated and nitroglycerin-mediated dilation or CPT of the brachial artery in the 2 populations. Patients with secondary RP were characterized by abnormalities in microvascular responses to reactive hyperemia, with a reduction in area under the curve adjusted for baseline perfusion, but not in time to peak response or peak perfusion ratio. Plasma ET-1, ADMA, VCAM-1, and MCP-1 levels were significantly elevated in secondary RP compared with primary RP. There was a significant negative correlation between ET-1 and ADMA values and measures of microvascular perfusion but not macrovascular endothelial function.
Secondary RP is characterized by elevations in plasma ET-1 and ADMA levels that may contribute to alterations in cutaneous microvascular function.
Arthritis & Rheumatism 08/2003; 48(7):1992-2000. · 7.87 Impact Factor
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Damon Duquaine,
Glenn A Hirsch,
Anjan Chakrabarti,
Zhenguo Han,
Chris Kehrer, Robert Brook,
Joy Joseph,
Anne Schott,
B Kalyanaraman,
Jeanette Vasquez-Vivar,
Sanjay Rajagopalan
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ABSTRACT: Adriamycin (ADR) is a commonly used chemotherapeutic agent that is believed to exert its effects through the generation of oxygen free radicals. We hypothesized that administration of a single dose of ADR results in endothelial nitric oxide synthase (eNOS)-dependent generation of superoxide (O2*-) and acute endothelial dysfunction. A single dose of ADR (10 mg/kg i.v.) administered to rabbits resulted in rapid attenuation of agonist-dependent responses to acetylcholine and calcium ionophore (A23187). In vitro exposure of ring segments to ADR for < 30 min resulted in O2*- generation measured by electron spin resonance (ESR) with the spin trap segments 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO) that was abolished by endothelial denudation and incubation with diphenyliodonium (DPI) (10 microM) but not L-NMMA (10 microM). Brachial artery flow-mediated dilation (FMD) in patients undergoing chemotherapy with ADR was markedly attenuated after a single dose of ADR (6.5 +/- 1.0 to 2.5 +/- 1.1% (p = 0.0004, time to end of infusion 27 +/- 8 min) while endothelial-independent dilatation with nitroglycerin was unchanged (16.3 +/- 3.1 and 14.33 +/- 2.1% respectively, p = 0.36). Serum nitrite and nitrate concentrations fell from 50 +/- 6 micromol/l pre-ADR to 33 +/- 6 micromol/l post-ADR infusion (p = 0.0005) while serum concentrations of CD141 thrombomodulin and von Willebrand factor (vWF) activity remained unchanged after ADR infusion (36 +/- 13 to 52 +/- 22% ng/ml versus 3.25 +/- 0.98 to 3.01 +/- 0.91%, respectively, p = NS for pre versus post for both). Doppler indices of diastolic function (IVRT, DT and E/A ratios) were not altered in response to ADR. In conclusion, ADR administration results in rapid depletion of systemic NO* levels and attenuation of agonist-dependent responses in rabbits and flow-mediated dilation in the brachial artery of humans. ESR measurements in rabbit ring suggest an endothelial origin for radical production via flavin-containing oxido-reductases such as eNOS or NADPH cytochrome P450 reductase. These findings may have implications for cardiovascular complications noted with ADR.
Vascular Medicine 05/2003; 8(2):101-7. · 1.46 Impact Factor
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ABSTRACT: Ambulatory blood pressure (BP) and heart rate (HR) were measured in a physically fit, normotensive postmenopausal African American woman, before and after 15 weeks of aerobic training. Mean BP, HR, and HR variability were normal at the outset and were further improved by training. Training had no effect on circadian BP variation, which exceeded gender- and age-specified limits, indicative of circadian hyperamplitude tension (CHAT). A 12-week treatment with the beta1-adrenoceptor blocker atenolol, 14 months post-training, normalized CHAT and HR variability and further reduced BP and HR. These results suggest beta1-adrenergic mediation of CHAT and its refractoriness to exercise training.
American Journal of Hypertension 10/2002; 15(9):827-30. · 3.18 Impact Factor
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ABSTRACT: Cutaneous microvascular responses to physiological stimuli are currently being investigated as indices of vascular function and to monitor responses to therapy. We attempted to systematically assess various microvascular cutaneous flow indices in response to reactive hyperaemia in control subjects and in patients with coronary artery disease (CAD), and to correlate these with brachial artery flow-mediated dilation (FMD). Groups of 24 healthy controls and 24 subjects with CAD underwent sequential brachial FMD determination in the dominant arm, and laser Doppler imaging to assess skin blood flow in the contralateral arm in response to reactive hyperaemia induced by cuff inflation and release. Laser Doppler values were expressed as: (a) AUC(5 min) (area under the curve over 5 min of release), (b) time to peak response, (c) % reactive hyperaemia, and (d) peak perfusion ratio. As expected, FMD was attenuated in CAD patients compared with controls (1.85+/-4.29% compared with 4.30+/-4.00%; P=0.05). Percentage reactive hyperaemia (CAD, 294+/-290%; controls, 501+/-344%; P=0.04) and the time to peak response as measured by laser Doppler imaging (CAD, 16.84+/-9.61 s; controls, 9.13+/-4.43 s; P=0.001) were significantly different between the CAD and control groups, while AUC(5 min) and the peak perfusion ratio did not show significant differences. Receiver operator curves for sensitivity/specificity analysis suggested that the time to peak response derived by laser Doppler imaging was superior to FMD for the diagnosis of CAD, with an overall specificity of 91.3% (positive predictive value of 89.4%) and a sensitivity of 73.7% (negative predictive value of 77.6%). In conclusion, laser Doppler-derived indices of microvascular flow do not correlate with conduit vessel responses. However, a time to peak response of >10 s as measured by laser Doppler imaging offers superior specificity for the diagnosis of CAD compared with brachial FMD.
Clinical Science 09/2002; 103(3):267-73. · 4.61 Impact Factor
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ABSTRACT: Aging is associated with progressive deterioration in endothelial function. We hypothesized that losartan may represent a useful therapeutic strategy to ameliorate endothelial function in aged subjects. Eighteen healthy older subjects (mean age 75 +/- 3 years) were prospectively randomized in a double-blind, crossover fashion to receive either losartan 50 mg/day or placebo for 6 weeks. Subjects were switched to the opposite arm after a 2- week washout period. Flow-mediated dilation (FMD) in the brachial artery and plasma levels of vascular cell adhesion molecule-1, intercellular adhesion molecule (ICAM), moncocyte chemoattractant 1 protein, and E-selectin were measured in both arms at the beginning and end of the 6-week period. Losartan resulted in a 6-mm Hg decrease in systolic blood pressure (from 130 +/- 12 to 124 +/- 13 mm Hg), which was no different from placebo (132 +/- 12 to 127 +/- 13 mm Hg). FMD increased from 3.1 +/- 0.6% to 3.9 +/- 0.6% after losartan, and decreased from 3.3 +/- 0.3% to 2.4 +/- 0.6% after placebo (p = NS for both). In contrast, losartan reduced circulating concentrations of vascular cell adhesion molecule 1 (750 +/- 73 to 572 +/- 39), ICAM (405 +/- 26 to 196 +/- 10), and moncocyte chemoattractant 1 protein (560 +/- 56 to 423 +/- 35) (p <0.01 for all by analysis of variance), but not E-selectin. On univariate analyses, the strongest predictor of baseline endothelial function and change in FMD with losartan was low-density lipoprotein. There was a negative correlation between baseline endothelial function and change in FMD in response to losartan (r(2) = -0.75, p = 0.0003). Baseline ICAM levels alone significantly correlated with low-density lipoprotein cholesterol (r(2) = 0.54, p = 0.02) and weakly correlated with total cholesterol (r(2) = 0.47, p = 0.05). Thus, administration of losartan for a duration of 6 weeks has favorable effects on inflammatory markers in healthy older subjects, but does not alter peripheral conduit endothelial function.
The American Journal of Cardiology 04/2002; 89(5):562-6. · 3.37 Impact Factor
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ABSTRACT: Nonsteroidal anti-inflammatory drugs are among the most widely prescribed medications. Their effect on blood pressure has been monitored, and many small studies have determined a potential relationship between their use and elevation of blood pressure. These drugs may affect blood pressure by inhibiting prostaglandin synthesis, which may affect arteriolar smooth muscle tone and natriuresis. Since many patients with conditions such as osteoarthritis require treatment and also have hypertension, even modest elevations in blood pressure or inhibition of antihypertensive medication efficacy resulting from non steroidal anti-inflammatory drugs can be of significant clinical and public health importance. This review finds that certain drugs (e.g., indomethicin, piroxicam, and naproxen) may cause clinically relevant elevations in blood pressure in hypertensive patients. Aspirin and sulindac do not appear to elevate blood pressure significantly, even in hypertensive patients. Ibuprofen and other nonsteroidal anti-inflammatory drugs appear to have an intermediate blood pressure effect. Cyclo-oxygenase-2 inhibitors such as refecoxib and celecoxib have been shown to cause mild elevations in blood pressure, but further studies are needed to evaluate the full magnitude and population distribution of this effect. (c)2000 by Le Jacq Communications, Inc.
Journal of Clinical Hypertension 11/2000; 2(5):319-323. · 1.83 Impact Factor
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ABSTRACT: OBJECTIVE: Oestradiol (E2) and its metabolites 2-hydroxyoestrone (2-OHE1) and 16alpha-hydroxyoestrone (16alpha-OHE1) are thought to curtail the greater oxidative stress found in the development and progression of disease conditions including atherosclerosis. We related oestrogen levels to F(2a)-isoprostane levels, a biomarker of oxidative stress. DESIGN AND PARTICIPANTS: Data were obtained from 1647 women, aged 47-57 years, participating in the fifth annual follow-up of the Study of Women's Health Across the Nation (SWAN), a study of the menopausal transition. MEASUREMENTS: Serum E2 and urinary 2-OHE1 and 16alpha-OHE1 concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and urinary F(2a)-isoprostanes were measured by enzyme immunoassay (EIA). RESULTS: F(2a)-isoprostane concentrations were elevated in women who smoked, a behaviour associated with increased oxidative stress, but not in stages of the natural menopause. Mean F(2a)-isoprostane concentrations among pre- and postmenopausal women who smoked were 1082 and 1064 pg/ml, respectively, values double those in pre- (343 pg/ml) and postmenopausal (379 pg/ml) nonsmoking women. 2-OHE1 and F(2a)-isoprostane concentrations were positively and highly correlated (partial correlations rho(Y|X) = 0.44 and rho(Y|X) = 0.43 in pre- and postmenopausal women, respectively). Similarly, 16alpha-OHE1 concentrations were positively and highly correlated with F(2a)-isoprostane concentrations (rho(Y|X) = 0.52 and rho(Y|X) = 0.59 in pre- and postmenopausal women, respectively). E2 was significantly correlated with F(2a)-isoprostanes only in postmenopausal women (rho(Y|X) = 0.20). Associations were adjusted for age, body mass index (BMI), race/ethnicity, lipids, physical activity level and alcohol consumption. CONCLUSIONS: This study does not support the commonly held hypothesis that levels of endogenous E2 or its oestrone metabolites favourably modify oxidative stress by decreasing F2(a)-isoprostane levels.
Sybil L. Crawford.
