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Biomedical subjects

Alan L Hinderliter

Publications and source records attributed to Alan L Hinderliter.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence and predictors of cardiovascular calcium in chronic kidney disease (from the Prospective Longitudinal RRI-CKD Study).

Although the determinants of cardiovascular calcium have been well described in dialysis patients, the prevalence and predictors in predialysis chronic kidney disease (CKD) are less known. One hundred six patients with CKD from the Renal Research Institute-CKD Study underwent multidetector computed tomography for the assessment of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve. Cardiovascular risk factors and renal function-related parameters (glomerular filtration rate, glomerular filtration rate slope, serum creatinine, serum urea nitrogen, hemoglobin, albumin, calcium, phosphate, and parathyroid hormone) were included in multivariate regression models to predict cardiovascular calcium. Prevalences of calcium deposition at the level of coronary arteries, thoracic aorta, aortic valve, and mitral valve were 69%, 46%, 39%, and 16%, respectively. On multivariate analysis, coronary artery calcium score was predicted by age (p < 0.0001), gender (p = 0.0001), diabetes (p = 0.024), and history of coronary artery disease (p = 0.016), but not by renal function related parameters. Similarly, renal function related parameters were not predictive of aortic or valvular calcium. In conclusion, predialysis CKD is associated with a high prevalence of cardiovascular calcium. The extent of cardiovascular calcium in patients with predialysis CKD is related to some of the traditional risk factors for atherosclerosis but not to indexes of abnormal renal function or progression in renal dysfunction.

Adult↗
PubMed2006

Depression and thyroid axis function in coronary artery disease: impact of cardiac impairment and gender.

BACKGROUND: Increased rates of depression are reported in coronary artery disease (CAD). In heart disease, depression increases disability, reduces quality of life, and increases mortality. HYPOTHESIS: The study was undertaken to examine the relationship between depression and thyroid axis function in patients with CAD. METHODS: In all, 73 patients with CAD, consecutively admitted to a cardiac rehabilitation hospital, were assessed for depression using the Hospital Anxiety and Depression scale (HADS). Blood was drawn for assessment of thyroid axis hormones and the N-amino terminal fragment of the pro-B-type natriuretic peptide (NT-pro BNP). RESULTS: The patients with CAD with depressive symptoms had a higher prevalence of cardiac failure (p = 0.04), higher NT-pro BNP concentrations (p = 0.02), and lower free triiodothyronine (T3) concentrations (p = 0.04) than patients with CAD but without depressive symptoms. They also showed a strong trend (p = 0.058) toward a higher incidence of the low T3 syndrome. Higher NT-pro BNP concentrations were related to lower total T3 concentrations (r = -0.294, p = 0.011) and to higher reverse T3 concentrations (r = 0.353, p = 0.002). In men, higher scores of depression were related to lower total T3 concentration (r = -0.289, p = 0.034) and to higher NT-pro BNP concentration (r = 0.380, p = 0.005). CONCLUSION: These findings suggest that symptoms of depression in patients with CAD are associated with changes in thyroid axis function and with cardiac impairment, especially in men.

Coronary Artery Disease↗
PubMed2006

The effects of periodontal therapy on vascular endothelial function: a pilot trial.

BACKGROUND: Chronic periodontal infection is associated with an increased risk of coronary heart disease. Although the mechanism responsible for the relationship between periodontal disease and cardiovascular events is not fully understood, it is hypothesized that the chronic inflammatory burden of periodontal disease may lead to impaired functioning of the vascular endothelium. METHODS: Twenty-two otherwise healthy adults with moderate to severe periodontitis who underwent complete mouth disinfection were evaluated to determine if periodontal therapy would result in improved endothelial function and a decrease in serum inflammatory markers. Subjects had measurements of periodontal disease severity, flow-mediated (endothelium-dependent), and nitroglycerin-mediated (endothelium-independent) dilation of the brachial artery, serum C-reactive protein (CRP) and interleukin 6 (IL-6), and serum total and high-density lipoprotein cholesterol levels on 2 baseline visits separated by 1 month and, again, 1 month after treatment. RESULTS: There were no significant changes in clinical periodontal measures, flow-mediated dilation, nitroglycerin-mediated dilation, CRP, IL-6, total cholesterol, or high-density lipoprotein cholesterol between the repeated baseline measurements. Periodontal treatment, however, resulted in significant improvements in periodontal pocketing, flow-mediated dilation, and serum IL-6, as well as a trend toward reduction in serum CRP; there were no significant changes in nitroglycerin-mediated dilation or in cholesterol levels. CONCLUSIONS: These results represent proof of concept that improvement in endothelial function, as measured by flow-mediated dilation of the brachial artery, may be possible through near-elimination of chronic oral infection and suggest that the conduct of a larger controlled trial is justified.

Adult↗
PubMed2006

Dietary sodium restriction alters postprandial ghrelin: implications for race differences in obesity.

OBJECTIVES: To examine the effect of sodium restriction on the appetite-stimulating hormone, ghrelin, as a function of race, salt sensitivity, and obesity. DESIGN: PARTICIPANTS completed two 4-day outpatient dietary interventions (moderate vs low sodium), and blood samples were drawn two hours after a controlled test meal under both conditions. SETTING: A university research laboratory and affiliated General Clinical Research Center. PARTICIPANTS: 37 women (18 Black, 19 White) and 18 men (9 Black, 9 White), aged 36-63 years. MEASURES: Cardiovascular function (blood pressure, heart rate, impedance-derived indices of cardiac output and peripheral resistance) was measured after a 20-minute rest before each test meal. Blood was drawn by intravenous forearm catheter two hours after each test meal and later assayed for ghrelin, leptin, and norepinephrine. RESULTS: After four days of sodium restriction, postprandial ghrelin increased in White men and women and Black men but decreased in Black women. Salt sensitivity, but not obesity, was also related to ghrelin response during sodium restriction; postprandial ghrelin tended to increase among salt-sensitive subjects during salt restriction but decrease among salt-resistant subjects during salt restriction. CONCLUSIONS: Satiety hormone dysregulation may play a role in: 1) the heightened obesity-related morbidity among Black women, in particular; 2) adherence to sodium-restricted diets; and 3) race differences in behavioral weight-loss interventions that include sodium restriction.

Adult↗
PubMed2005

Changes in plasma volume associated with mental stress ischemia in patients with coronary artery disease.

Psychological stress has been shown to trigger angina and myocardial ischemia in patients with coronary artery disease. However, the mechanisms by which stress may trigger cardiac events has yet to be fully elucidated. Twenty five patients underwent radionuclide ventriculography during a multiple stress challenge. Plasma volume was assessed during rest and at the end of the stress task. Flow-mediated dilatation was also measured. Controlling for endothelial function and medications, patients with ischemia had greater reductions in plasma volume than non-ischemic patients. Reduced plasma volume may be one mechanism by which mental stress may increase the risk for acute coronary events.

Aged↗
PubMed2005

Impaired endothelial function in coronary heart disease patients with depressive symptomatology.

OBJECTIVES: The purpose of this study was to assess whether depressive symptomatology was associated with vascular endothelial dysfunction in patients with coronary heart disease (CHD). BACKGROUND: In patients with CHD, the presence of depression is associated with a two to four times increased risk of mortality, but the disease pathways involved are uncertain. Endothelial dysfunction is an established risk factor for cardiovascular events in patients with CHD. METHODS: Flow-mediated dilation (FMD) of the brachial artery, a measure of endothelial function, was assessed in 143 patients (99 men, 44 women), ages 40 to 84 years (mean age, 63 +/- 10 years), with documented CHD. RESULTS: Patients with significant depressive symptomatology, as indicated by a Beck Depression Inventory (BDI) score > or = 10 (n = 47) showed attenuated FMD (p = 0.001) compared with patients that were not depressed (BDI < 10; n = 96). The use of antidepressant medication was associated with improved FMD (p < 0.05). CONCLUSIONS: The increased risk of cardiovascular events in CHD patients with elevated symptoms of depression may be mediated, in part, by endothelial dysfunction.

Adult↗
PubMed2005

Lack of beneficial effects of clonidine in the treatment of premenstrual dysphoric disorder: results of a double-blind, randomized study.

OBJECTIVES: To test the effects of clonidine in comparison with active placebo on premenstrual symptoms, mood scores and norepinephrine (NE) concentration, in women with premenstrual dysphoric disorder (PMDD). METHODS: Twelve women with prospectively confirmed PMDD were randomly assigned to oral 0.3 mg/day clonidine, as an active treatment, or 10 mg/day loratadine, as an active placebo, for 2 months each using a double-blind, cross-over design. NE concentration, premenstrual symptom ratings and mood scales were measured on three occasions: at pretreatment, after clonidine treatment and after placebo treatment. All patients were free of current psychiatric co-morbidity and medication use. RESULTS: There were no significant differences between clonidine and placebo for mood scales or premenstrual symptom ratings, though clonidine significantly suppressed NE concentration and produced more side effects in comparison with placebo. CONCLUSION: Compared with an active placebo clonidine demonstrated no beneficial changes in mood and premenstrual symptoms in women with PMDD.

Administration, Oral↗
PubMed2005

Histories of sexual abuse are associated with differential effects of clonidine on autonomic function in women with premenstrual dysphoric disorder.

In women meeting strict criteria for premenstrual dysphoric disorder (PMDD), we examined whether clonidine, an alpha2-adrenergic receptor (AR) agonist, would have different effects on sexually abused versus non-abused PMDD women for measures of autonomic nervous system function. Twelve women meeting prospective, DSM-IV criteria for PMDD, five of whom had a history of sexual abuse, participated in a randomized, placebo-controlled, double-blind, cross-over design study, comparing 2 months of on oral clonidine (0.3 mg/day) with 2 months on active placebo. During the luteal phase that preceded randomization and following each two-month challenge, women were tested for cardiovascular measures at rest and in response to mental stress, and for resting plasma norepinephrine (NE) concentrations as well as beta1 and beta2-AR responsivity using the isoproterenol sensitivity test. Results revealed that in comparison to placebo, clonidine significantly reduced plasma norepinephrine concentrations, increased both beta1- and beta2-AR responsivity, and reduced resting and stress heart rate (HR) and blood pressure (BP) (p < 0.05) in all PMDD women. With clonidine, sexually abused PMDD women exhibited greater decreases in resting and stress-induced HR (p < 0.01) and stress-induced systolic BP (p < 0.05), while non-abused PMDD women exhibited greater reductions in plasma NE concentration (p = 0.07), and greater increases in beta2-AR responsivity (p < 0.05) than abused PMDD women. These results suggest PMDD women with and without a history of sexual abuse respond differently to a clonidine challenge in measures reflecting autonomic nervous system functioning, indicating that abuse may modify presynaptic alpha2-AR function in PMDD.

Administration, Oral↗
PubMed2005

Oxytocinergic activity is linked to lower blood pressure and vascular resistance during stress in postmenopausal women on estrogen replacement.

Estrogen administration results in increased release of the oxytocin (OT) prohormone reflected by increases in oxytocin intermediate peptide (OT Int) in both animal models and humans, and sequential treatment of ovariectomized rats with estrogen/progesterone then progesterone withdrawal leads to increased hypothalamic OT mRNA. Blood pressure (BP) reductions have been related to increased exogenous and endogenous OT in rats and to higher endogenous OT activity in premenopausal women, but not previously in postmenopausal women. Thus, we used plasma obtained at rest and during a speech stressor from 54 postmenopausal women who participated in a 6-month randomized trial of oral conjugated estrogens vs. placebo to examine effects of estrogen replacement therapy (ERT) on plasma OT and OT Int levels and their relationships to changes in BP during the trial. ERT alone and with progesterone (but not placebo) led to significant increases in plasma levels of OT Int, but no change in plasma OT levels. Women showing greater increases in OT Int during treatment showed greater decreases in BP and total vascular resistance during a series of behavioral stressors compared to women with moderate or no increases in OT Int, even after controlling for effects related to treatment condition or to changes in plasma estradiol. The findings suggest that enhanced oxytocinergic activity may contribute to BP decreases associated with ERT in more responsive postmenopausal women.

Adult↗
PubMed2004

Association between exercise capacity and left ventricular geometry in overweight patients with mild systemic hypertension.

The purpose of this study was to determine the relation between left ventricular (LV) geometry and exercise capacity in unmedicated, hypertensive patients. Analysis of the data revealed peak oxygen consumption (ml kg(-1) min(-1)) for concentric hypertrophy (corrected mean +/- SE 23.5 +/- 1.2) was significantly less (F = 3.68, p <0.02) than the concentric remodeling (28.1 +/- 1.2) and normal (27.3 +/- 0.6) geometries. The LV geometric pattern was found to be associated with exercise capacity in unmedicated, hypertensive patients, such that patients with concentric hypertrophy showed reduced capacity.

Echocardiography↗
PubMed2004

Effects of daily stress on autonomic cardiac control in patients with coronary artery disease.

Emotional stress has been implicated in the development and progression of coronary artery disease, with 1 proposed causal pathway being changes in cardiac autonomic tone. One hundred thirty-five patients with coronary artery disease underwent 48 hours of ambulatory electrocardiographic monitoring and completed activity and mood diaries every 20 minutes while awake. Random-effects model analyses associated higher levels of negative emotions (e.g., anger, stress, sadness) with decreases in high- and low-frequency power, whereas higher levels of positive emotion were related to an increase in low-frequency power, independent of age, posture, and medications.

Coronary Artery Disease↗
PubMed2004

Cardiovascular effects of 6 months of hormone replacement therapy versus placebo: differences associated with years since menopause.

OBJECTIVE: In response to post-Women's Health Initiative dialog regarding individualized hormone replacement therapy (HRT), this study evaluates cardiovascular and neuroendocrine effects of HRT versus placebo in postmenopausal women grouped according to time since menopause. STUDY DESIGN: Resting and stress blood pressure (BP), hemodynamic, plasma catecholamine, and cholesterol levels were obtained in 69 women randomly assigned to placebo or active HRT in a 6-month double-blind study. Analyses evaluated if treatment effects differed among those postmenopausal less than 5 years versus 5 years or more. RESULTS: Compared with the placebo-treated and HRT > or =5 groups, the HRT < 5 group showed reduced BP (P<.0007) and trends toward reduced vascular resistance and norepinephrine (P<.07). HRT > or =5 group generally did not differ from placebo. CONCLUSION: Reduced BP and sympathetic tone are evident in some HRT users, with diminishing benefit after the initial postmenopausal years. Time since menopause may be an important consideration in making individualized patient treatment decisions.

Adult↗
PubMed2004

Ethnic differences in left ventricular structure: relations to hemodynamics and diurnal blood pressure variation.

BACKGROUND: Previous studies have suggested that African Americans have a greater left ventricular relative wall thickness than whites with similar levels of blood pressure (BP), whereas other investigators have documented an attenuated nocturnal decline in BP and early remodeling of the resistance vessels in African Americans. METHODS: To further evaluate the contributions of diurnal BP variation and vascular remodeling to ethnic differences in left ventricular geometry, we measured ambulatory BP, systemic hemodynamics, minimum forearm vascular resistance, and left ventricular structure in a biracial sample of 171 men and women between the ages of 25 and 45 years. RESULTS: Despite similar resting BPs, African Americans had a greater indexed peripheral resistance, a greater minimal forearm vascular resistance, and a smaller nocturnal decline in BP than white subjects. African Americans also had a greater left ventricular relative wall thickness (0.41 +/- 0.07 v 0.38 +/- 0.08, P =.048) and a trend toward a greater indexed left ventricular mass (41.1 +/- 8.7 v 38.6 +/- 8.6 g/m(2.7), P =.087). Ethnic differences in relative wall thickness were no longer significant when adjusted for either indexed peripheral resistance (P =.173) or sleep systolic BP (P =.124). CONCLUSIONS: In our cohort of young men and women, African Americans had a greater left ventricular relative wall thickness than whites with similar levels of resting BP. This early concentric remodeling of the left ventricle in African Americans may be mediated, in part, by hemodynamic influences, including a greater peripheral vascular resistance and a smaller nocturnal decline in BP.

Adult↗
PubMed2004

Relationship between exercise systolic blood pressure and left ventricular geometry in overweight, mildly hypertensive patients.

OBJECTIVE: To examine the association between the graded exercise systolic blood pressure (SBP) response and left ventricular (LV) geometric structure in patients with untreated mild hypertension. PARTICIPANTS: The study included 80 sedentary, overweight patients (43 female and 37 male) with unmedicated high normal blood pressure or stage 1-2 hypertension. METHODS: An echocardiogram was used to determine LV mass and the relative wall thickness (RWT) in relation to the chamber dimension. Participants performed a maximal graded exercise test, and the SBP was recorded at workloads of 2, 4 and 6 metabolic equivalents and at peak exercise. Separate statistical models were used to determine the influence of LV mass indexed for height(2.7) (LVMIh) and RWT on submaximal exercise SBP and peak exercise SBP, controlling for resting SBP, age, gender, ethnicity and body mass index. RESULTS: A greater RWT was associated with a higher submaximal SBP level (P = 0.038). Neither LVMIh (P = 0.989) nor the interaction of RWT and LVMIh (P = 0.787) were related to the submaximal SBP. None of the main or interaction effects of RWT and LVMIh were associated with the peak exercise SBP level. CONCLUSION: Increases in RWT were associated with higher submaximal exercise SBP responses in a sample of overweight, unmedicated hypertensives. These results suggest that RWT is an important determinant of the association between cardiac mass and exercise SBP response.

Adult↗
PubMed2004

Transdermal versus oral estrogen therapy in postmenopausal smokers: hemodynamic and endothelial effects.

OBJECTIVE: To test the hypothesis that, in postmenopausal smokers, transdermal estrogen would be more effective than oral estrogen in reducing blood pressure (BP) and vascular and norepinephrine responses to stress and in increasing endothelial function and vascular beta2-adrenoceptor responsivity. METHODS: By using a randomized, double-blind, placebo-controlled design, 82 healthy postmenopausal smokers were tested before and after 6 months of therapy with transdermal estrogen (0.05 mg/d) plus a progestin (2.5 mg/d; n = 31), oral conjugated equine estrogen (0.625 mg/d) plus a progestin (2.5 mg/d; n = 30), or placebo (n = 21). Dependent measures included resting and stress-induced increases in BP, total peripheral resistance, and plasma norepinephrine, as well as endothelial function and beta-adrenoceptor responsivity. RESULTS: When compared with placebo, the transdermal estrogen group showed more consistent reductions in total peripheral resistance at rest and in response to mental stress than the oral estrogen group. Only the transdermal group showed treatment-related reductions in behavioral stress norepinephrine, baseline rest, and behavioral stress BP levels, and increases in vascular beta2-adrenoceptor responsivity and endothelium-dependent vasodilation. Posttreatment concentrations of serum estradiol and estrone were lower and the serum estradiol/estrone ratio closer to pre-menopausal values in the group receiving transdermal estrogen compared with oral estrogen. CONCLUSION: Six months of transdermal estrogen therapy is associated with greater reductions in measures reflecting vascular sympathetic tone than oral estrogen therapy in healthy postmenopausal smokers. Thus, transdermal estrogen may be associated with a more favorable risk/ benefit ratio in postmenopausal smokers, a group at high risk of osteoporosis and cardiovascular disease.

Administration, Cutaneous↗
PubMed2004

Postprandial ghrelin is elevated in black compared with white women.

Ghrelin, a gut-brain peptide that signals hunger, is normally suppressed after meals. Subnormal suppression of postprandial ghrelin, previously noted in obese, insulin-resistant individuals, may contribute to increased food intake. Given the ethnic disparities in obesity and obesity-related cardiovascular morbidity in the United States, the present study compared a single postprandial ghrelin measure in 43 women (22 white, 21 black). Each completed a rigorously controlled 4-d dietary intervention designed to maintain weight and constant daily sodium and potassium intake (220 mEq Na, 40 mEq K). Two hours after consuming a test meal of identical content, blood samples were drawn to assess postprandial ghrelin, leptin, and norepinephrine; resting cardiovascular function was measured; and a 24-h urinary cortisol sample was obtained. Independent of body mass index, postprandial ghrelin was significantly higher in black vs. white women, and higher ghrelin was associated with higher cortisol in blacks, who failed to show the expected inverse relation between ghrelin and central obesity seen in whites. Higher ghrelin was correlated with higher blood pressure but lower norepinephrine in obese women. These findings suggest subnormal postprandial ghrelin suppression (or faster ghrelin rebound) in black women, especially the obese, that might play a role in their increased prevalence of obesity and cardiovascular disorders.

Adult↗
PubMed2003

Effects of the oral endothelin-receptor antagonist bosentan on echocardiographic and doppler measures in patients with pulmonary arterial hypertension.

OBJECTIVES: The purpose of this study was to investigate the effects of bosentan (125 or 250 mg twice daily) on echocardiographic and Doppler variables in 85 patients with World Health Organization class III or IV pulmonary arterial hypertension (PAH). BACKGROUND: Bosentan, an orally active dual endothelin-receptor antagonist, improves symptoms, exercise capacity, and hemodynamics in patients with PAH. METHODS: Patients had primary pulmonary hypertension (84%) or PAH associated with connective tissue disease. Of these, 29 patients received placebo and 56 received bosentan (1:2 randomization). Six-minute walk tests and echocardiograms were performed at baseline and after 16 weeks of treatment. RESULTS: Baseline characteristics were similar in the placebo and bosentan groups, and echocardiographic and Doppler findings were consistent with marked abnormalities of right ventricular (RV) and left ventricular (LV) structure and function that were due to PAH. The treatment effect on 6-min walking distance was 37 m in favor of bosentan (p = 0.036). Treatment effects of bosentan compared with placebo on other parameters were as follows: Doppler-derived cardiac index = +0.4 l/min/m(2) (p = 0.007), LV early diastolic filling velocity = +10.5 cm/s (p = 0.003), LV end-diastolic area = +4.2 cm(2) (p = 0.003), LV systolic eccentricity index = -0.12 (p = 0.047), RV end-systolic area = -2.3 cm(2) (p = 0.057), RV:LV diastolic areas ratio = -0.64 (p = 0.007), Doppler RV index = -0.06 (p = 0.03), and percentage of patients with an improvement in pericardial effusion score = 17% (p = 0.05). CONCLUSIONS: Bosentan improves RV systolic function and LV early diastolic filling and leads to a decrease in RV dilation and an increase in LV size in patients with PAH.

Administration, Oral↗