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D M Herrington

Publications and source records attributed to D M Herrington.

At least 19 recordsLinked to original sources
PubMed2006

Hormone replacement therapy is associated with increased C-reactive protein in women with Type 2 diabetes in the Diabetes Heart Study.

AIMS: Increased levels of inflammatory biomarkers, especially C-reactive protein (CRP), are associated with increased risk for cardiovascular disease (CVD) events, such as myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. Medical interventions that increase CRP levels, such as hormone replacement therapy (HRT) in post-menopausal women, are under increasing scrutiny. The effect of HRT on CRP levels in women with Type 2 diabetes (T2DM) is not well documented, and conflicting conclusions have been reported. The aim of this study was to determine the influence of HRT on women with diabetes in a large cross-sectional study. METHODS: Three hundred and twenty-seven post-menopausal women with T2DM from the Diabetes Heart Study participated. Current use of HRT was determined and serum CRP levels were measured using a high-sensitivity ELISA kit. Generalized estimating equation methods were used to assess the relationship of multiple clinical and lifestyle (e.g. smoking) measures on CRP levels including differences between women taking HRT (HRT+) and not taking HRT (HRT-). RESULTS: Overall serum CRP levels were strongly associated with body mass index (P < 0.0001) and age (P < 0.0001). Of the women, 243 were not using HRT and 84 were using HRT. HRT+ and HRT- women did not differ significantly in measures of clinical traits, with the exception of higher mean low-density lipoprotein cholesterol in HRT- women (P = 0.004). In all models tested, HRT+ women had significantly higher circulating CRP levels, with P-values ranging from 0.0045 to 0.010. CONCLUSIONS: In this study of serum CRP concentration as a function of HRT in women with Type 2 diabetes, there was consistent evidence for increased circulating CRP levels in women receiving oestrogen-containing HRT. Whether HRT-induced increases in CRP can account for the adverse cardiovascular effects of HRT remains to be established; however, based on these data, there is little reason to believe that diabetic women would be spared from such an effect.

Body Mass Index↗
PubMed2005

The impact of ethnicity and sex on subclinical cardiovascular disease: the Diabetes Heart Study.

AIMS/HYPOTHESIS: African-Americans with type 2 diabetes and access to adequate healthcare are at lower risk of clinical coronary artery disease than are white diabetic patients. We evaluated whether ethnic differences in subclinical cardiovascular disease, coronary and carotid artery calcified plaque and carotid artery intima-medial thickness (IMT) were present in members of The Diabetes Heart Study families. SUBJECTS AND METHODS: In a bi-racial cohort of 1,180 individuals from families enriched for members with type 2 diabetes, we calculated coronary and carotid artery calcified plaque using fast-gated helical computed tomography, and measured carotid artery IMT and clinical risk factor profiles. Generalised estimating equations were used to test for an association between measures of subclinical cardiovascular disease and ethnicity and sex. RESULTS: After adjustment for age, ethnicity and kidney function, African-Americans had significantly lower amounts of coronary artery calcified plaque (mean+/-SE) (866+/-158 vs 1,915+/-135, respectively; p=0.0466) and carotid artery calcified plaque (179+/-51 vs 355+/-27, respectively; p=0.0240) relative to whites, despite having increased carotid IMT (0.71+/-0.01 vs 0.67+/-0.004 cm, respectively; p=0.0007), and higher blood pressure, albuminuria and HbA1c. Sex-specific analyses revealed that African-American men had significantly lower coronary and carotid artery calcified atheroma than white men. In women, ethnic differences in calcified carotid artery plaque, but not coronary artery plaque, were observed. CONCLUSIONS/INTERPRETATION: In families enriched for members with type 2 diabetes, African-American men had markedly lower levels of coronary and carotid artery calcified plaque than white men, despite increased carotid artery IMT and conventional risk factors. These findings suggest that susceptibility to subclinical cardiovascular disease differs markedly according to ethnicity and sex.

Adult↗
PubMed2005

Effects of hormone therapy on C-reactive protein and IL-6 in postmenopausal women: a review article.

The results of the Women's Health Initiative, showing an increase in coronary heart disease events in postmenopausal women on estrogen and medroxyprogesterone acetate, have created considerable interest in finding an underlying mechanism that may confer cardiovascular risk in women on hormone therapy (HT). Inflammation is thought to play a key role in the progression of atherosclerosis. C-reactive protein (CRP) is an inflammatory marker that has been studied as a predictor of future coronary risk. Interleukin 6 (IL-6) is felt to be an important cytokine in the inflammatory cascade and instrumental in CRP expression. The purpose of this article is to summarize the observational and randomized studies that examine the difference in IL-6 and CRP concentrations with respect to oral versus transdermal hormone therapy. We also review studies looking at differences in CRP levels based on the progestin component of HT and trials examining the effect of estrogen agonists on IL-6 and CRP. In our review, we found CRP levels to be elevated in the majority of postmenopausal women on oral HT. There was no correlation between IL-6 and CRP levels. Studies examining the effect of progestins produced varying results. Transdermal estrogen, in contrast, showed no elevation in levels of IL-6 or CRP alone or with the addition of progestins. Selective estrogen receptor agonists (SERMs) did not demonstrate an effect on CRP levels, although tibolone did increase CRP in one reviewed trial. Questions remain about the role of progestins and transdermal HT therapy in the inflammatory process and the underlying mechanism of CRP activation. More research is needed to understand how HT may be involved in the inflammatory process.

Administration, Cutaneous↗
PubMed2004

The combination oral and nutritional treatment of late-onset diabetes mellitus (CONTROL DM) trial results.

OBJECTIVE: To examine the effect of short-term improvements in glycaemic control on brachial artery endothelial function as a marker of cardiovascular health. METHODS: Persons with Type 2 diabetes who were poorly controlled on oral therapy were randomly assigned to monotherapy with repaglinide or combination therapy with repaglinide plus metformin. Brachial artery flow-mediated vasodilation was assessed by ultrasonography at randomization and following 16 weeks of therapy. The primary outcome was change in brachial artery endothelial function from baseline. Comparison of randomized groups was a secondary aim. RESULTS: Eighty-six participants were randomized, and 83 were followed to study completion. Post occlusion brachial artery vasodilation was 3.74% at baseline and 3.82% following 16 weeks of therapy (P = 0.77). The treatment effect was 0.08% (95% CI: -0.48%, 0.64%). No difference was seen between treatment groups (P = 0.69). Overall, A1C was reduced from 8.3% to 7.0%, with a greater reduction in the combination therapy group (from 8.4% to 6.7%) than in the monotherapy group (from 8.3% to 7.3%, p for difference between groups = 0.01). Statistically significant reductions were observed in fasting glucose, and plasminogen activator inhibitor-1. Statistically significant increases were observed for fasting insulin, uric acid, weight and BMI. CONCLUSIONS: Brachial artery endothelial function was not influenced by short-term improvements in glycaemic control. The CONTROL DM group was successful in lowering A1C. Future research should explore more intensive and longer-lasting improvements in glycaemic control on endothelial function. Some data previously published in abstract form (Diabetes 2001; 50 (Suppl. 2): A217).

Administration, Oral↗
PubMed2004

The effects of smoking on estradiol metabolism.

Smoking remains a major health problem especially among women and it influences estrogen metabolism and the risk for multiple estrogen sensitive outcomes. Many indirect effects of smoking exist through the ability of the by-products to modify a variety of drugs, enzymes, and hormones. The results of several in vitro studies have shown that constituents of cigarette smoke have significant effects on production and metabolism of estrogens. In some cases, such as osteoporosis and endometrial cancer, smoking appears to attenuate the effects of estrogen. However, for other outcomes such as breast cancer, venous thromboembolic events (VTE), and coronary heart disease (CHD), the relationship between smoking and estrogen exposure is less defined. Based on the preponderance of evidence, smokers are likely to require higher doses of hormone replacement therapy (HRT) to achieve comparable clinical effect to that observed in nonsmokers. However, uptitrating the dose of HRT in smokers to achieve a desired systemic level or clinical response may simultaneously increase risk for adverse effects that are primarily driven by hepatic rather than systemic exposure. The healthy benefits from smoking cessation should be expressed to women who choose to use HRT, and every effort should be made to encourage them to stop smoking so that they can be effectively treated with the lowest possible dose of HRT.

Adult↗
PubMed2003

Statin therapy in the heart and estrogen/progestin replacement study.

AIM: Limited data exists to guide secondary prevention in postmenopausal women with coronary heart disease (CHD). Treatment with HMG-CoA reductase inhibitors (statins) is likely to be beneficial for these patients. Yet, clinical trial results are conflicting. Moreover, significant interactions may exist between statins and hormone replacement therapy (HRT) that may complicate this approach. METHODS: In a post hoc analysis of the HERS trial, patients who were taking a statin were compared to those who were not. Subjects were randomized to HRT or placebo. Statin therapy was not controlled by the trial investigators, but may have been prescribed by the patients' primary physicians. Use of statins was monitored throughout the trial. The primary outcome was the composite of myocardial infarction and death resulting from CHD, with all-cause mortality and venous thromboembolism (VTE) as secondary outcome measures. RESULTS: At baseline, 1004 subjects were taking a statin, with 1234 subjects randomized to receive HRT, and 1237 to receive placebo. Baseline statin use was associated with lower rates of the primary outcome (MI or fatal CHD, RH=0.78, 95% CI 0.61 to 0.99, p=0.044), and all-cause mortality (RH=0.74, 95% CI 0.56 to 0.99, p=0.04). Statin therapy was associated with a reduced incidence of VTE in both the HRT group and the placebo arm. The negative effect of HRT on the primary outcome seen in the 1st year of treatment was much reduced among baseline statin users and was no longer statistically significant (RH=1.34, 95% CI 0.63 to 2.86, p=0.45). CONCLUSION: Data from HERS supports the use of statins for secondary prevention in postmenopausal women with a history of cardiovascular disease. Statins may attenuate the increased cardiovascular risk of hormone replacement therapy.

Aged↗
PubMed2003

No effect of HRT on health-related quality of life in postmenopausal women with heart disease.

AIM: Previous clinical studies suggest hormone replacement therapy (HRT) alleviates menopausal symptoms and may improve health-related quality of life (HRQL). Most studies on HRT and HRQL were limited in duration (12 months or less) and scope (few and non-standard HRQL measures). The aim of this paper is to assess HRQL in the Estrogen Replacement and Atherosclerosis (ERA) trial. METHODS: A subset of women within a randomized, blinded, placebo-controlled secondary prevention trial has been studied in outpatient and community settings at 5 US sites. A total of 246 postmenopausal women with angiographically documented heart disease (mean age 66 years, 83% Caucasian) were enrolled in the ERA trial. Participants received either 0.625 mg/day conjugated equine estrogen only, estrogen plus 2.5 mg/day medroxyprogesterone acetate, or placebo. HRQL was assessed using validated questionnaire instruments at baseline and follow-up (mean 3.2 years of trial). Physical and mental functioning, life satisfaction, depressive symptoms, urinary incontinence, sleep disturbance, and frequency and intensity of physical symptoms were evaluated. RESULTS: In this group of women with established coronary disease, active therapy was not significantly associated with more favorable outcomes for any HRQL. The estrogen-only group reported more urinary incontinence than the placebo group (p<0.05). Analyses restricted to adherent women (those who took > or = 80% of pills) showed a similar pattern of results, showing that the estrogen only group reported significantly higher urinary incontinence compared to placebo (p<0.01). CONCLUSION: The hormone replacement regimens in the ERA trial did not improve HRQL of postmenopausal women with heart disease.

Adult↗
PubMed2001

The incidence of unrecognized myocardial infarction in women with coronary heart disease.

BACKGROUND: Several cohort studies in populations without coronary heart disease have demonstrated that up to 40% of incident myocardial infarctions are clinically unrecognized. OBJECTIVE: To determine the incidence of unrecognized myocardial infarction in women with coronary heart disease in the Heart and Estrogen/progestin Replacement Study (HERS). DESIGN: Randomized, double-blind, placebo-controlled trial of conjugated estrogens plus medroxyprogesterone or identical placebo with 4.1 years of follow-up. SETTINGS: Outpatient and community settings at 20 U.S. clinical centers. PATIENTS: 2763 postmenopausal women younger than 80 years of age with coronary heart disease and an intact uterus. MEASUREMENTS: Annual electrocardiograms were obtained for all participants during follow-up (mean, 4.1 years) and were evaluated by using the NOVACODE computer algorithm and visual confirmation. A total of 13 715 electrocardiograms were obtained. Suspected unrecognized myocardial infarctions were investigated by comparing a participant's previous surveillance electrocardiograms with the electrocardiograms obtained from all of her intervening hospitalizations. Characteristics of patients with recognized and unrecognized myocardial infarction were compared. RESULTS: Among the 256 nonfatal myocardial infarctions, 11 were unrecognized (4.3% [95% CI, 2.2% to 7.6%]). Seven occurred in women assigned to placebo and 4 occurred in women assigned to hormone therapy (P > 0.2). Women with unrecognized myocardial infarction were less likely to have diabetes mellitus or previous angina and were more likely to have had previous bypass surgery compared with women who had clinically recognized myocardial infarction. CONCLUSION: The incidence of unrecognized myocardial infarction in women with coronary disease was far lower than that observed in previous studies of populations without coronary heart disease.

Aged↗
PubMed2001

Statins, hormones, and women: benefits and drawbacks for atherosclerosis and osteoporosis.

Clinical trials have shown that 3-hydoxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, known as statins, significantly reduce the risk of both primary and secondary coronary heart disease events. Although these trials have included few women, the evidence suggests that statins are as effective in women as in men. The addition of hormone replacement therapy to statin therapy augments lowering of low- density lipoprotein cholesterol, but may not increase the favorable effects on clinical events achieved with statins alone. Finally, new data suggest that statins may also reduce the risk of osteoporotic fractures, a provocative finding still in need of verification by clinical trials.

Arteriosclerosis↗
PubMed2001

An adaptive template-matching method and its application to the boundary detection of brachial artery ultrasound scans.

We developed an adaptive template-matching method for vessel wall boundary detection in brachial artery ultrasound (US) scans. The computer-aided identification of lumen-intima and media-adventitia boundaries of the brachial artery US scan is a critical step for flow-mediated vasodilator response measurement, which has become an increasingly important tool in both clinical and research applications. The adaptive template we propose in this paper is a combination of two parameterized Gaussian envelopes that approximates the US pulse envelope. The algorithm for template matching is cast as a constrained nonlinear least squares problem. A best match between the template and the observed US scan line signal results in a set of optimum parameters of the adaptive template, and the location of the boundaries is directly computed from these parameters. We present the results of applying our method to synthetic and clinical data, showing that the adaptive template-matching method provides superior accuracy in detecting the media-adventitia boundaries of both the near wall and the far wall of the vessel to that of conventional edge-detection methods.

Algorithms↗
PubMed2001

Cardiac cycle-dependent changes in aortic area and distensibility are reduced in older patients with isolated diastolic heart failure and correlate with exercise intolerance.

OBJECTIVES: The goal of this study was to determine if cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility are associated with exercise intolerance in elderly patients with diastolic heart failure (DHF). BACKGROUND: Aortic compliance declines substantially with age. We hypothesized that a reduction in cardiac cycle-dependent changes in thoracic aortic area and distensibility (above that which occurs with aging) could be associated with the exercise intolerance that is prominent in elderly diastolic heart failure patients. METHODS: Thirty subjects (20 healthy individuals [10 < 30 years of age and 10 > 60 years of age] and 10 individuals > the age of 60 years with DHF) underwent a magnetic resonance imaging (MRI) study of the heart and proximal thoracic aorta followed within 48 h by maximal exercise ergometry with expired gas analysis. RESULTS: The patients with DHF had higher resting brachial pulse and systolic blood pressure, left ventricular mass, aortic wall thickness and mean aortic flow velocity, and, compared with healthy older subjects, they had a significant reduction in MRI-assessed cardiac cycle-dependent change in aortic area and distensibility (p < 0.0001) that correlated with diminished peak exercise oxygen consumption (r = 0.79). After controlling for age and gender in a multivariate analysis, thoracic aortic distensibility was a significant predictor of peak exercise oxygen consumption (p < 0.04). CONCLUSIONS: Older patients with isolated DHF have reduced cardiac cycle-dependent changes in proximal thoracic aortic area and distensibility (beyond that which occurs with normal aging), and this correlates with and may contribute to their severe exercise intolerance.

Adult↗
PubMed2001

Cardiovascular trials of estrogen replacement therapy.

An impressive body of evidence has suggested that estrogen therapy should be helpful to slow the pathogenesis or progression of atherosclerosis. Estrogen's favorable effects on lipids and endothelial function, coupled with extensive observational epidemiology and data from animal models of atherosclerosis, persuaded many that hormone replacement therapy (HRT) would be helpful for both primary and secondary prevention of coronary disease. Recently, several randomized clinical trials of HRT have been completed, and several more are currently under way. These trials include both primary and secondary prevention cohorts and use clinical as well as anatomic manifestations of atherosclerosis as outcomes. These trials are producing surprising and controversial results that will radically alter contemporary understanding of the role of HRT for cardiovascular disease prevention. This review briefly describes the findings of the Heart and Estrogen/Progestin Replacement Study, the Estrogen Replacement and Atherosclerosis Trial, and other recently completed clinical trials. Trials that are under way are also described and discussed.

Arteriosclerosis↗
PubMed2001

Invited review: Pharmacogenetics of estrogen replacement therapy.

There are a number of genetic factors that likely modulate both the beneficial and adverse effects of estrogen. An important domain of consideration is the relationship of estrogen and thrombosis risk. Gene polymorphisms among the key elements of the coagulation and fibrinolytic cascade appear to influence the effects of estrogen on risk for venous thromboembolic events and possibly arterial thrombosis as well. Emerging data also suggest that allelic variants in the estrogen receptor-alpha may modulate estrogen's effects, especially with respect to bone and lipid metabolism.

Coronary Disease↗
PubMed2001

Estrogen replacement and brachial artery flow-mediated vasodilation in older women.

It remains unclear whether estrogen therapy (with or without progestin) improves endothelial function in older postmenopausal women with or at risk for coronary heart disease. To address this issue, we analyzed brachial artery flow-mediated vasodilation in the Cardiovascular Health Study, a longitudinal study of cardiovascular risk factors in subjects over 65 years of age. At the tenth annual Cardiovascular Health Study examination, 1662 women returned for follow-up. Eighteen percent (n=291) were current users of estrogen replacement, most of whom (75.9%, n=221) took unopposed estrogen. Brachial artery ultrasound examinations measuring vasodilation in response to a flow stimulus (hyperemia) were performed on 1636 women. There were no statistical differences in brachial flow-mediated vasodilator responses between users and nonusers, even after adjustment for potential confounders. Absence of an effect was most notable in women over 80 years old and in those with established cardiovascular disease. However, among women without clinical or subclinical cardiovascular disease or its risk factors, there was a significant association between hormone replacement therapy use and flow-mediated vasodilator responses (P=0.01). Among older postmenopausal women, favorable vascular effects of estrogen may be limited to those who have not yet developed atherosclerotic vascular disease. These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease.

Aged↗
PubMed2001

Brachial flow-mediated vasodilator responses in population-based research: methods, reproducibility and effects of age, gender and baseline diameter.

BACKGROUND: Brachial artery ultrasound has been proposed as an inexpensive, accurate way to assess cardiovascular risk in populations. However, analysis and interpretation of these data are not uniform. METHODS: We analysed the relationship between relative and absolute changes in brachial artery diameter in response to flow-mediated dilation and age, gender and baseline diameter among 4,040 ultrasound examinations from subjects aged 14 to 98 years. RESULTS: Reproducibility studies demonstrated intra- and interreader and intrasubject correlations from 0.67 to 0.84 for repeated measures of per cent change in diameter. Per cent change in diameter after flow stimulus was 3.58 +/- 0.10% (mean +/- standard deviation). Corresponding values for baseline diameter and absolute change in diameter were 4.43 +/- 0.87 mm and 0.15 +/- 0.01 mm, respectively. Baseline diameter and its variance were inversely related to per cent change in diameter (P< 0.001). In contrast, absolute change in diameter was more uniform throughout the range of baseline diameters. Baseline diameter was directly related, and per cent change in diameter inversely related, to age (P < 0.001 for all three measures). Time to maximum vasodilator response increased with age (P < 0.001). Women (n=2,315) had significantly larger per cent change in diameter than men (n=1,725) (P < 0.001). However, after adjustment for age and baseline diameter, per cent and absolute change were 5% smaller in women than men (P < 0.05 for both). In multivariate analysis, age was overwhelmingly the most important determinant of absolute change in diameter (P < 0.001). CONCLUSIONS: Automated analysis of brachial flow-mediated vasodilator responses is both feasible and reproducible in large-scale clinical and population-based research.

Adolescent↗