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Pamela Ouyang

Publications and source records attributed to Pamela Ouyang.

At least 19 recordsLinked to original sources
PubMed2006

Hormone replacement therapy and the cardiovascular system lessons learned and unanswered questions.

Cardiovascular disease is the leading cause of death among women in the U.S., exceeding breast cancer mortality in women of all ages. Women present with cardiovascular disease a decade after men, and this has been attributed to the protective effect of female ovarian sex hormones that is lost after menopause. Animal and observational studies have shown beneficial effects of hormone therapy when it is initiated early in the perimenopausal period or before the development of significant atherosclerosis. However, randomized, placebo-controlled trials in older women have not shown any benefit in either primary prevention or secondary prevention of cardiovascular events, with a concerning trend toward harm. This review outlines the lessons learned from the basic science, animal, observational, and randomized trials, and then summarizes yet-unanswered questions of hormone therapy and cardiovascular risk.

Animals↗
PubMed2006

Randomized trial of hormone therapy in women after coronary bypass surgery. Evidence of differential effect of hormone therapy on angiographic progression of disease in saphenous vein grafts and native coronary arteries.

Clinical trials indicate that hormone therapy (HT) does not decrease cardiovascular disease events or angiographic coronary disease progression. The effects of HT on SVG vessels are unknown. To determine whether postmenopausal hormone therapy started after coronary bypass surgery (CABG) decreases saphenous vein graft (SVG) disease, we conducted a multicenter randomized placebo-controlled angiographic study of estradiol+/-medroxyprogesterone started within 6 months of CABG in 83 postmenopausal women. Angiographic and intravascular ultrasound (IVUS) assessment at 6 and 42 months was planned to assess SVG disease progression. The study was stopped early following publication of the Women's Health Initiative Estrogen/Progestin study. Eighty-three subjects underwent a 6-month angiogram with 63 undergoing IVUS. Forty-five subjects completed the 42-month angiogram (20 underwent 42-month IVUS). In analysis of paired 6- and 42-month angiogram and IVUS studies, HT slowed angiographic progression of SVG disease assessed by mean percent stenosis (p<0.001), minimal lumen diameter (p=0.029), and total plaque volume (p=0.006). In contrast, HT accelerated disease progression in non-bypassed native coronary arteries (minimum lumen diameter, p=0.01). SVG disease and closure occurred in 38% subjects within 1-year post-CABG. The groups had similar frequency of cardiovascular events expect for angioplasty that occurred in eight HT compared to one placebo subject (p<0.05). In HT subjects angioplasty was indicated for native coronary arterial stenoses while in the placebo subject angioplasty was indicated for SVG stenosis. This study suggests that hormone treatment may slow SVG disease progression while accelerating atherosclerosis in non-bypassed native coronary arteries.

Coronary Angiography↗
PubMed2006

A randomized, double-blind trial comparing the effects of amlodipine besylate/benazepril HCl vs amlodipine on endothelial function and blood pressure.

Evidence suggests that renin-angiotensin-aldosterone system inhibition ameliorates endothelial dysfunction. The authors examined the effect of amlodipine besylate/benazepril HCl combination treatment compared with amlodipine besylate monotherapy in modulating endothelial dysfunction. This multicenter, double-blind, 12-week study randomized 70 hypertensive subjects with at least one other endothelial dysfunction risk factor to amlodipine besylate/benazepril HCl (5/20 mg/d force-titrated to 5/40 mg/d) or amlodipine besylate monotherapy (5 mg/d force-titrated to 10 mg/d). Both the combination and monotherapy produced significant median increases from baseline in percentage flow-mediated vasodilation (2.0% and 1.2%, respectively) and percentage change in percent flow-mediated vasodilation (25% and 16%, respectively). These improvements were numerically larger with combination treatment, but between-group differences did not achieve statistical significance. Reductions in systolic and diastolic blood pressure were significantly greater (P=.0452/P=.0297) with combination treatment (-18.6/-12.3 mm Hg) than with monotherapy (-14.8/-9.1 mm Hg). A highly positive correlation between change in systolic blood pressure and change in percent of flow-mediated vasodilation was demonstrated only for combination treatment.

Aged↗
PubMed2005

Usefulness of serum endothelin levels in predicting death and myocardial infarction but not coronary progression in postmenopausal women with coronary disease (from the Women's Angiographic Vitamin and Estrogen [WAVE] study).

We performed a cohort study of 392 postmenopausal women who had coronary disease to assess whether baseline serum endothelin-1 level predicts angiographic disease progression, nonfatal myocardial infarction, or death. Angiographic progression was defined as the annualized change in minimal lumen diameter of all qualifying lesions for each patient. Twenty-nine patients died or had a myocardial infarction during follow-up. Each picogram per milliliter increase in endothelin-1 was associated with a 1.8-fold increased risk of death or myocardial infarction. After adjustment for potential confounders, endothelin-1 remained a predictor of clinical events but was not correlated with angiographic progression.

Aged↗
PubMed2005

Effect of exercise on blood pressure in older persons: a randomized controlled trial.

BACKGROUND: Because of age-related differences in the cause of hypertension, it is uncertain whether current exercise guidelines for reducing blood pressure (BP) are applicable to older persons. Few exercise studies in older persons have evaluated BP changes in relation to changes in body composition or fitness. METHODS: This was a 6-month randomized controlled trial of combined aerobic and resistance training; controls followed usual care physical activity and diet advice. Participants (aged 55-75 years) had untreated systolic BP (SBP) of 130 to 159 mm Hg or diastolic BP (DBP) of 85 to 99 mm Hg. RESULTS: Fifty-one exercisers and 53 controls completed the trial. Exercisers significantly improved aerobic and strength fitness, increased lean mass, and reduced general and abdominal obesity. Mean decreases in SBP and DBP, respectively, were 5.3 and 3.7 mm Hg among exercisers and 4.5 and 1.5 mm Hg among controls (P < .001 for all). There were no significant group differences in mean SBP change from baseline (-0.8 mm Hg; P=.67). The mean DBP reduction was greater among exercisers (-2.2 mm Hg; P=.02). Aortic stiffness, indexed by aortofemoral pulse-wave velocity, was unchanged in both groups. Body composition improvements explained 8% of the SBP reduction (P = .006) and 17% of the DBP reduction (P<.001). CONCLUSIONS: A 6-month program of aerobic and resistance training lowered DBP but not SBP in older adults with mild hypertension more than in controls. The concomitant lack of improvement in aortic stiffness in exercisers suggests that older persons may be resistant to exercise-induced reductions in SBP. Body composition improvements were associated with BP reductions and may be a pathway by which exercise training improves cardiovascular health in older men and women.

Aged↗
PubMed2005

Ethnic differences in coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND: There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. METHODS AND RESULTS: Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score >0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P<0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P<0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score >0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). CONCLUSIONS: We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed.

Black or African American↗
PubMed2005

Skin tissue cholesterol assay correlates with presence of coronary calcium.

BACKGROUND: Keratinocytes maintain cholesterol homoeostasis using LDL and HDL-scavenger receptor pathways implicated in atherosclerosis. We tested whether skin tissue cholesterol (SkTC) is associated with subclinical atherosclerosis, assessed using carotid intima-medial thickness (IMT) and coronary artery calcification (CAC). METHODS: Two hundred and twenty two subjects were recruited from the Baltimore site of the Multi-Ethnic Study of Atherosclerosis (MESA). Baseline MESA examination included fasting blood collection, IMT measurement by B-mode ultrasound and CAC determination by helical CT. SkTC was measured using the Cholesterol 1, 2, 3 kit (IMI Inc., Canada). RESULTS: SkTC was significantly higher if CAC was present in Caucasians (p = 0.04) but not African-Americans. SkTC was not significantly correlated with IMT in either group. Using multiple logistic regression adjusting for age, sex and serum lipids, a 1-standard deviation higher SkTC was associated with 187% higher odds of the presence of CAC in Caucasians (p < 0.01) but no significant difference in odds for African-Americans. In subjects in whom CAC was present, the extent of CAC was not related to the SkTC in multiple linear regressions. CONCLUSIONS: SkTC was associated with the presence of CAC independently of serum lipids/lipoproteins in Caucasians but not African-Americans. SkTC may provide a useful indicator of subclinical atherosclerosis in Caucasians.

Black or African American↗
PubMed2005

Long-term hormone replacement therapy does not cause increased platelet activation.

BACKGROUND: Observational studies have shown apparently lower ischemic coronary disease risk in postmenopausal women receiving hormone replacement therapy (HRT). However, several recent studies have shown an increase in ischemic cardiac events when HRT is initiated in postmenopausal women with known coronary artery disease. It is postulated that estrogen may result in increased platelet aggregation. METHODS: We evaluated platelet activation, as measured by flow cytometric analysis using P selectin and PAC1 as activation markers, and aggregation, as measured by standard platelet aggregation using platelet-rich plasma, in 27 postmenopausal women (17 HRT, 10 placebo) who were participants in 2 placebo-controlled randomized angiographic trials evaluating the effect of HRT on coronary atherosclerosis or saphenous vein graft disease. All women had received HRT or placebo for >2 years and were on aspirin therapy. The estrogen component was either conjugated equine estrogen or 17beta-estradiol. RESULTS: Patients on HRT and those on placebo had comparable degrees of platelet aggregation when measured using various doses of agonists (adenosine diphosphate and epinephrine). There were no significant differences in levels of platelet activation measured by flow cytometry. CONCLUSION: We conclude that long-term HRT does not appear to cause increased platelet activation and aggregation in women with coronary artery disease. There may be increased platelet activation in the early period after HRT initiation; however, this was not assessed in this study.

Aged↗
PubMed2005

Oxygen pulse during exercise is related to resting systolic and diastolic left ventricular function in older persons with mild hypertension.

BACKGROUND: The mechanisms responsible for impaired cardiovascular hemodynamics during exercise among persons with milder forms of hypertension are not well documented. We examined the relationship of oxygen pulse during exercise, a correlate of stroke volume, with echocardiographic indices of resting left ventricular function to determine whether abnormal contractility and relaxation are related to abnormal cardiovascular dynamics during exercise among such persons. METHODS: Subjects were 44 men and 55 women ages 55 to 75 years with mild hypertension but who were otherwise healthy. Resting left ventricular systolic and diastolic functions were assessed with 2-dimensional Doppler echocardiography and tissue Doppler imaging. Oxygen pulse (millimeters per beat) at rest and during multistage treadmill testing was derived from measurements of oxygen consumption and heart rate. The slope of oxygen pulse between successive exercise stages was calculated. RESULTS: After a steep rise in oxygen pulse from rest to stage 1 of exercise, a markedly diminished oxygen pulse slope was seen between subsequent exercise stages. In stepwise regression analysis, the increase in the slope of oxygen pulse from rest to stage 1 was explained by a greater lean body mass (57%, P < .001) and a larger left atrial size (2%, P < .001). After exercise stage 1, the increase in the slope of oxygen pulse was explained by sex (24%, P < .001), higher mitral E/A ratio (6%, P < .001), and higher mitral annular systolic velocity (6%, P < .001). CONCLUSIONS: These results suggest that a blunted oxygen pulse response to exercise among older persons with milder forms of hypertension may reflect impaired left ventricular stroke volume changes during exercise secondary to subtle abnormalities in both systolic and diastolic left ventricular functions.

Aged↗
PubMed2005

Sex differences in left ventricular function in older persons with mild hypertension.

BACKGROUND: Epidemiologic studies suggest that women are at increased risk of developing heart failure secondary to hypertension. Other studies have documented sex differences in left ventricular systolic and diastolic function in the presence of pressure overload states such as seen in aortic stenosis and hypertension. It is less clear if sex differences are present among older persons with mild hypertension. METHODS: One hundred seven healthy subjects, aged 55 to 75 years, with blood pressures ranging from 130 to 159 mm Hg systolic and/or 85 to 99 mm Hg diastolic, were examined by standard echocardiography and the newer modalities of tissue Doppler and color M-mode imaging. RESULTS: Women had a lower peak mitral annular systolic velocity (Sm), 8.9 (95% CI 8.4-9.5) cm/s versus 10.2 (95% CI 9.6-11.0) cm/s, (P < .01) than men. Among women, increasing age was associated with a reduction in diastolic function. For every decade of age, peak early mitral annular diastolic velocity (Em) declined by 1.6 cm/s (P < .01), mitral inflow velocity of propagation (Vp) declined by 26% (P < .01), E/Vp ratio increased by 20% (P = .03), and E/Em ratio increased by 11% (P = .04) in women. No age-associated changes were seen in men. CONCLUSIONS: As revealed by newer echocardiographic imaging modalities, women with mild hypertension showed greater reductions in systolic and diastolic function as they aged compared with men. Our findings are consistent with the increased risk older women have of developing heart failure because of hypertension.

Age Factors↗
PubMed2005

Exercise and risk factors associated with metabolic syndrome in older adults.

BACKGROUND: Older people with elevated blood pressure (BP) often have metabolic syndrome, a clustering of central obesity, insulin resistance, dyslipidemia, and hypertension. Exercise reduces many of these risk factors. This study examined whether the benefits of exercise on cardiovascular and metabolic disease risk factors are mediated by exercise-induced changes in fitness or body composition. METHODS: Randomized controlled trial, comprising 6 months of exercise training, conducted between July 1999 and November 2003. Participants included men and women (n =115) aged 55 to 75 years with untreated systolic blood pressure (SBP) of 130 to 159 or diastolic blood pressure of (DPB) 85 to 99 mm Hg. Fitness measures included BP, lipids, lipoproteins, insulin, and glucose; peak oxygen uptake and muscle strength; and body composition measured by anthropometry, dual-energy x-ray absorptiometry, and magnetic resonance imaging. RESULTS: A total of 51 men and 53 women completed the trial. Exercise significantly increased aerobic and muscle fitness, lean mass, and high-density lipoprotein cholesterol and reduced total and abdominal fat. DBP was reduced more among exercisers. There were no associations among changes in fitness with risk factors. Reductions in total body and abdominal fat and increases in leanness, largely independent of weight loss, were associated with improved SBP, DBP, total cholesterol, very low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), and insulin sensitivity. At baseline, 42.3% of participants had metabolic syndrome. At 6 months, nine exercisers (17.7%) and eight controls (15.1%) no longer had metabolic syndrome, whereas four controls (7.6%) and no exercisers developed it (p =0.06). CONCLUSIONS: Although exercise improved fitness, the reductions in total and abdominal fatness and increase in leanness were more strongly associated with favorable changes in risk factors for cardiovascular disease and diabetes, including those that constitute metabolic syndrome.

Age Factors↗
PubMed2005

Exercise effects on bone mineral density relationships to changes in fitness and fatness.

BACKGROUND: Weight loss typically reduces bone mineral density (BMD). Exercise may preserve or increase BMD even while reducing fatness. We examined the relationships among exercise-induced changes in fitness and fatness with BMD. DESIGN: Randomized controlled trial conducted between July 1999 and November 2003. PARTICIPANTS: Men and women (n =115) aged 55 to 75 years. INTERVENTION: Six months of exercise training. MAIN OUTCOME MEASURES: Fitness measured as peak oxygen uptake and muscle strength, body composition by anthropometry, dual-energy x-ray absorptiometry, and magnetic resonance imaging. RESULTS: A total of 51 men and 53 women completed the trial. Exercise increased aerobic and strength fitness and lean body mass, and reduced general and abdominal obesity. BMD did not change among men in either group. Among women exercisers, there were reductions in total skeleton BMD (p =0.02) and greater trochanter BMD (p =0.02). By bivariate correlation, among women, increased femoral neck BMD was associated with increased aerobic fitness (p =0.01) and with reduced body weight (p =0.02) and BMI (p =0.02). In the final regression model, 13% of the change in femoral neck BMD was explained by the change in aerobic fitness (p <0.01). Among the men, increased total hip BMD and femoral shaft BMD were associated with increased lean mass and lower-body strength. In the final regression models, the change in lean mass explained 9% of the variance in total hip BMD (p =0.04). The change in lean mass explained 20% of the change in femoral shaft BMD (p <0.01), and the change in lower-body strength explained an additional 6% (p <0.04). CONCLUSIONS: When examined by group assignment, 6 months of exercise had no effect on BMD among men, and reduced BMD among women. When examined by change in fitness and fatness, women who had the greatest increases in aerobic capacity and men who had the greatest increases in strength and lean mass were more likely to increase their BMD. Exercise-induced reductions in fatness did not lead to bone loss.

Absorptiometry, Photon↗
PubMed2005

A novel method for assessing arterial endothelial function using phase contrast magnetic resonance imaging: vasoconstriction during reduced shear.

We investigated whether endothelial-dependent arterial constriction during reduced shear can be measured using phase contrast magnetic resonance imaging (PCMRI). A cross-section of the femoral artery was acquired during a 5-minute distal occlusion in 33 subjects. Systolic shear rate and radius were measured from the velocity profile via a best-fit parabola. Systolic shear rate decreased immediately after cuff inflation (404 +/- 78 to 233 +/- 75 sec(-1) p < .0001). Radius decreased at 2 min into inflation (3.52 +/- .41 to 3.43 +/- .42 mm, p < .0001). In conclusion, arterial constriction during reduced flow can be measured using PCMRI. This new method may add important information toward a comprehensive evaluation of endothelial function.

Adult↗
PubMed2004

Hormone therapy and antioxidant vitamins do not improve endothelial vasodilator function in postmenopausal women with established coronary artery disease: a substudy of the Women's Angiographic Vitamin and Estrogen (WAVE) trial.

We measured flow-mediated dilation (FMD) by high-resolution brachial ultrasound in 61 women who participated in the Women's Angiographic Vitamin and Estrogen (WAVE) trial, a randomized controlled trial. There were no significant differences in the baseline demographics of women receiving hormone therapy (0.625 mg/day of conjugated equine estrogen plus 2.5mg of medroxyprogesterone acetate for women who had not had a hysterectomy) or placebo; or vitamins (400 IU of Vitamin E and 500 mg of Vitamin C twice daily) or placebo. Baseline FMD was impaired in all subjects (3.3+/-7.6%). Neither hormone therapy (4.1+/-5.2% at baseline, 4.2+/-5.0% at 3 months, and 4.1+/-6.5% at 34 months) nor antioxidant vitamins (3.0+/-8.3% at baseline; 3.5+/-4.6% at 3 months; 3.1+/-7.6% at 34 months) improved FMD (all p-values=NS). Endothelium-independent vasodilation, induced by nitroglycerin (NTG) was similar at baseline and was not affected by either therapy. In univariate and multivariate analysis, neither hormone therapy nor antioxidant vitamins were associated with FMD. Women with established coronary artery disease have impaired flow-mediated vasodilation of the brachial artery that does not improve after 3 months or up to 34 months of treatment with postmenopausal hormone therapy or antioxidant vitamins.

Aged↗
PubMed2004

Why is flow-mediated dilation dependent on arterial size? Assessment of the shear stimulus using phase-contrast magnetic resonance imaging.

Flow-mediated dilation (FMD) is strongly dependent on arterial size, but the reasons for this phenomenon are poorly understood. We have previously shown that FMD is greater in small brachial arteries because the shear stress stimulus is greater in small brachial arteries. However, it is unclear why the shear stimulus is greater in small arteries. Furthermore, this relationship has not been investigated in other, differently sized arterial beds. Postischemic systolic shear stress and resulting FMD were evaluated in the brachial and femoral arteries of 24 young, healthy adults using phase-contrast magnetic resonance imaging. Arterial shear and radius were calculated from the velocity profile via a best-fit parabola before and after occlusion. Summing the velocity pixels provided hyperemic systolic flow. FMD was proportional to hyperemic shear in the brachial and femoral arteries (P < 0.0001, r = 0.60). Hyperemic systolic flow was proportional to radius2 (P < 0.0001, r = 0.93). Applying this relationship to the Poiseuille equation (shear is proportional to flow/radius3) shows that hyperemic shear is proportional to radius2/radius3 and, therefore, explains why hyperemic shear is proportional to 1/radius. We conclude that FMD is proportional to hyperemic systolic shear stress in both the brachial and the femoral arteries. The hyperemic shear stimulus for FMD is greater in small arteries due to the dependence of postischemic systolic flow on radius squared. Therefore, greater FMD in small arteries does not necessarily reflect better conduit artery endothelial function. Evaluating the shear stimulus using phase-contrast magnetic resonance imaging enhances the understanding of mechanisms underlying FMD.

Adult↗
PubMed2004

Postmenopausal hormone therapy is associated with atherosclerosis progression in women with abnormal glucose tolerance.

BACKGROUND: Abnormal glucose tolerance (AGT; diabetes or impaired glucose tolerance) is associated with increased risk of cardiovascular disease, especially in women. Cardiovascular disease rates in women increase after menopause. The Women's Health Initiative found that postmenopausal hormone therapy (PHT) increased the risk of cardiovascular disease and that effects in diabetic women did not differ from those in women without diabetes. In this study, we hypothesized that PHT would have a worse effect on disease among women with AGT. METHODS AND RESULTS: We randomly assigned 423 postmenopausal women with angiographically defined atherosclerosis (321 women had exit angiograms) with (n=140) or without (n=181) AGT to receive estrogen, estrogen plus progestin, or a placebo for 2.8+/-0.9 years. LDL was lower and HDL and triglycerides were higher after PHT in non-AGT and AGT women, but more adverse changes occurred in C-reactive protein and fibrinogen in women with AGT (P=0.11 and P=0.02 for interactions). PHT had no effect on fasting glucose or insulin concentrations in women without AGT, but in women with AGT, fasting glucose levels, insulin concentration, and insulin resistance as assessed by the HOMA (homeostasis model) calculation decreased slightly (P=0.28, P=0.25, P=0.14 for interaction, respectively). Atherosclerotic progression was greater in women with AGT. Atherosclerotic progression in previously nondiseased segments was enhanced by PHT to a greater extent in women with AGT (P=0.11 for interaction). CONCLUSIONS: PHT is associated with a worsening of coronary atherosclerosis and exacerbation of the profile of inflammatory markers in women with AGT. Therefore, PHT is not warranted for use in diabetic women. Further study is needed to explore the improvement in insulin resistance and glycemia that appears to occur with PHT in women with AGT.

Adult↗