D Herrington

..Given the importance of detecting gene-gene and gene-environment interactions, a rigorous, comprehensive comparison of performance and limitations of available interaction detection methods is warranted...

..We sought to examine the individual and combined effects of estrogen/progestin therapy versus lovastatin on lipids and flow-mediated vasodilation in postmenopausal women with heart disease...

..To summarize recent data regarding the role of estrogen receptor-alpha polymorphisms in determining the response to estrogen therapy or the risk of clinical cardiovascular events...

..We sought to assess the relation between lower extremity arterial compliance and presence of angiographically defined coronary artery disease...

..Therefore, clinicians should continue to make use of family history to augment risk stratification and emphasize established forms of prevention for their patients with, or at risk for, cardiovascular disease...

..Although effects of statins on cardiovascular outcomes are well established in men, fewer data exist for women. Furthermore, the effects of statins plus hormone replacement therapy (HRT) on cardiovascular outcomes are uncertain...

..If factor V Leiden genotyping becomes less expensive, it could be cost effective to screen for the presence of the mutation before instituting HRT in women with coronary disease...

..More detailed haplotype and genome-wide studies of many of the major HRT clinical trial cohorts are currently underway and these efforts promise to clarify many outstanding issues concerning estrogen action and cardiovascular disease...

..Trials that are under way are also described and discussed...

..It remains unknown whether droloxifene can confer a true cardiovascular benefit...

..These data emphasize the importance of ongoing efforts to determine the role of hormone replacement therapy for primary prevention of cardiovascular disease...

..Noninvasive measures of arterial compliance may be useful for the detection of subclinical atherosclerosis...

..The HERS results remind us of the need for clinical trials to evaluate both the benefits and risks of new therapies. They also illustrate how much more we need to know about the cardiovascular effects of hormone replacement therapy...

..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...

..The extent to which selective estrogen receptor modulators and phytoestrogens share in the beneficial and potentially harmful effects of estrogen is not yet established...

..Control Clin Trials 2000;21:257-285..

..We assessed the predictive value of FMD for incident CVD events in the Multi-Ethnic Study of Atherosclerosis (MESA)...

..02)], and the MS demonstrated a similar trend [odds ratio, 1.98 (95% CI, 0.90 to 4.33)]. CONCLUSIONS: Among postmenopausal women with coronary heart disease, the presence of diabetes predicted disease progression, but the MS did not...

..Estrogen has been shown to enhance endothelial-dependent flow-mediated vasodilation (FMD) in healthy and younger women. The effect of estrogen on older and less healthy postmenopausal women with atherosclerosis is unclear...

..In postmenopausal women with coronary disease, increased levels of baseline pulse pressure are associated with subsequent progression of coronary atherosclerosis in postmenopausal women. HRT had no detectable effect on pulse pressure...

..Use of hormone replacement therapy produced a small, statistically significant increase in PP. Further research is necessary to determine the clinical utility of PP as a potential therapeutic target...

..53 +/- 0.1 to 0.57 +/- 0.1 (P = 8.1 x 10(-10)), suggesting a modest but detectable effect of this gene on the phenotype of CorCP in type 2 diabetic patients...

..The increased CVD risk in African American women may be related to impaired endothelial function. It remains to be determined whether African American women may uniquely benefit by interventions designed to improve endothelial health...

..While the APOE locus shows evidence of contributing to CRP levels, no evidence of CRP gene polymorphism association with CRP levels was observed...

..We have identified a novel region of the ESR1 gene that may contain important functional polymorphisms in relation to susceptibility to T2DM and/or diabetic nephropathy...

..We sought to replicate the finding that genetic variants in the nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with QT interval duration in a type 2 diabetes-enriched sample of European ancestry...

..We wanted to assess the predictive value of plasma sphingomyelin levels for incident coronary heart disease (CHD) events in the Multi-Ethnic Study of Atherosclerosis...

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..In contrast, IL-6 levels are not affected by estrogen or estrogen plus progestin. Estrogen-induced changes in CRP are not associated with progression of atherosclerosis...

..Costs of community-based recruitment were less than hospital-based recruitment; however, screening costs were higher. Overall, screening and recruitment averaged $2508 per randomized participant. Control Clin Trials 2001;22:13-25..

..This article will review the findings to date of these long-term randomized clinical trials of HRT for prevention or treatment of CHD...

..Determining gender-specific differences in CRP may alter how CRP levels are interpreted and used to determine risk...

..We assessed the hypothesis that FMD predicts incident cardiovascular events in a population-based cohort of older adults...

..This study sought to quantitate the available observational evidence on whole grain intake and clinical cardiovascular events...

..Evidence suggests that interleukin-1 receptor-associated kinase-1 (IRAK1), fundamental in the toll-like receptor pathway (TLR), may play a more specific role in atherosclerosis...

..Whole-grain intake has been shown to be inversely associated with cardiovascular events, but an association with atherosclerosis is less well established...

..Many elderly patients with heart failure exhibit a normal left ventricular ejection fraction (HFNEF). It is unknown whether FMAD is severely reduced in the elderly with HFNEF...

..In the Multi-Ethnic Study of Atherosclerosis (MESA), we estimated the proportion of intermediate-risk participants whose risk status might change based on additional testing using CRP and/or CAC score...

..More research is warranted concerning the physiological and clinical consequences of hyperuricemia, especially in blacks...

..We tested associations of the growth factors VEGF, FGF-2, HGF and PDGF-BB with coronary artery calcium scores and cardiovascular events (CVD) in type 2 diabetes mellitus (T2DM)...

..It is unclear whether these genetic variants remain relevant in subjects with underlying conditions such as diabetes that are associated with prolonged QT interval...

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..Based on population survey data, 95% of American women are considered at low risk based on FRS...

..The aim of this study was to determine the relationship between brachial flow-mediated dilation (FMD) and carotid intima-media thickness (IMT) in a large multi-ethnic elderly cohort...

..We assessed the effect of HT on soluble cell adhesion molecules in the Estrogen Replacement and Atherosclerosis trial...

..We assessed the association of FMD and the presence or absence of subclinical and clinical CVD in a population based cohort of older adults...

..Limited biochemical and clinical evidence suggest a link between IL-10 and coronary heart disease (CHD). However, more data are needed to clarify the relationship between IL-10 and risk for CHD events...

..The relation between dietary fish intake and brachial artery measures, including brachial artery flow-mediated dilation (FMD), has not been well established across sex and racial-ethnic groups...

..In diabetes, it remains unclear whether the coronary artery calcium (CAC) score provides additional information about total mortality risk beyond traditional risk factors...

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..We analyzed the HERS data to determine whether there were specific subgroups of women who responded differently to treatment, either during the first year or in the overall study...

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..The goal of this study was to determine the relationship between resting blood pressure (BP) and C-reactive protein (CRP) in a multi-ethnic cohort of men and women from the Multi-Ethnic Study of Atherosclerosis (MESA)...

..Epidemiological studies suggest that levels of C-reactive protein (CRP) predict cardiovascular disease (CVD). We have evaluated the relationship between CRP and subclinical CVD in a study cohort at high risk of CVD...

..In addition to the events trial, a carotid ultrasound substudy was established in 1993 to be conducted concurrently to determine whether hormone therapy affects the progression of the underlying atherosclerotic process...

..This study sought to determine if this augmentation extends to HRT regulation of E-selectin and C-reactive protein (CRP) and to explore possible mechanisms by which this polymorphism might influence estrogen action...

..However, it is unknown whether a similar relationship exists in younger individuals...

..We examined the relationship between coronary artery disease, measured by coronary artery calcified plaque (CAC), and the duration of QRS, JT, and QT intervals, among predominantly type two diabetic participants...

..Thus, interventions that combine medical treatments with psychosocially based interventions may be most effective for women at risk for impaired HRQL...

..Long-term randomized clinical trials are needed to more definitively address whether oral L-arginine supplementation could be advantageous for vascular health...

..CONCLUSIONS: In our study, 2 weeks of HeartBar supplementation in subjects with hypercholesterolemia showed no favorable effects on endothelial or platelet function...

..The inclusion of pharmacogenomic studies in large clinical trials and other more innovative investigative methods may provide greater clarity of the potential role for genotyping in the treatment of patients with hypertension...

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..Muscadine grape seeds have high concentrations of polyphenolic compounds with antioxidant and other properties that would be expected to have favorable effects on endothelial function...

..CONCLUSIONS: MMP activity likely contributes to the development of acute coronary syndromes and may be an important therapeutic target for future drug development...

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..It will be important to replicate these findings in other studies...

..This study suggests that hormone treatment may slow SVG disease progression while accelerating atherosclerosis in non-bypassed native coronary arteries...

..To determine whether the mechanisms of C-reactive protein production differ depending on the presence or absence of a progestin in the regimen...

..Estradiol reduced progression of ultrasonographic carotid disease in a randomized trial. No trials of unopposed estrogen for prevention of lower extremity arterial disease or aortic aneurysm have been conducted...

..Dietary patterns may influence cardiovascular disease risk through effects on inflammation and endothelial activation...

..The aim was to examine the association between intakes of total fiber and fiber from different dietary sources and progression of coronary-artery atherosclerosis among women with established CAD...

..We investigated whether elevated CRP is a risk factor for ischemic stroke independent of carotid IMT and studied the interaction between CRP and IMT...

..However, limited data exist on the effect of fish intake on actual measures of progression of coronary artery atherosclerosis...

..These results are consistent with previous findings that triglyceride measurements are more strongly related to clinical vascular events in women than in men...

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..The association of coronary heart disease (CHD) with subpopulations of triglyceride (TG)-rich lipoproteins and high-density lipoproteins (HDL) is established in men, but has not been well characterized in women...

..Whether these relationships are entirely independent of obesity is unclear. This association might be one of the mechanisms explaining the relationship between sleep apnea, hypertension, and cardiovascular disease...

..In conclusion, thigh compliance measured with a simple-to-use, fully automated device independently predicts aerobic fitness in patients with a wide range of cardiovascular risk but without CHD...

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..Microalbuminuria is a risk factor for coronary heart disease (CHD). It occurs most commonly in the settings of diabetes and hypertension. The mechanisms by which it increases CHD risk are uncertain...

..Determining specific genetic and/or environmental factors that influence a person's risk of disease may help doctors reduce risk for disease and reveal new treatments for disease. (End of Abstract) ..

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..In addition, identification of variants that predispose to atherosclerosis may suggest novel pathophysiologic pathways that could be explored as potential targets for new therapeutic interventions. ..

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..In addition, this information could lead to fundamentally important new knowledge about mechanisms of estrogen action, regulation of HDL cholesterol, and pathogenesis of CHD. ..

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..Determining specific genetic and/or environmental factors that influence a person's risk of disease may help doctors reduce risk for disease and reveal new treatments for disease. (End of Abstract) ..