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Biomedical subjects

D S Sheps

Publications and source records attributed to D S Sheps.

At least 19 recordsLinked to original sources
PubMed2001

Sex differences in chest pain in patients with documented coronary artery disease and exercise-induced ischemia: Results from the PIMI study.

BACKGROUND: Sex differences in the pathophysiologic course of coronary artery disease (CAD) are widely recognized, yet accurate diagnosis of coronary artery disease in women remains challenging. METHODS: To determine sex differences in the clinical manifestation of CAD, we studied chest pain reported during daily activities, exercise, and mental stress in 170 men and 26 women. All patients had documented CAD (>50% narrowing in at least 1 major coronary artery or prior myocardial infarction) and all had 1-mm ST-segment depression on treadmill exercise. We collected psychologic test results, serum samples (potassium, epinephrine, norepinephrine, cortisol, b-endorphin, and glucose), and cardiac function, sensory threshold, and autonomic function data at specified times before, during, or after exercise and mental stress tests to assess measures of depression, anxiety, and neurohormonal and thermal pain perception. RESULTS: Women reported chest pain more often than men during daily activities (P =.04) and during laboratory mental stressors (P =.01) but not during exercise. Men had lower scores than women on measures of depression, trait anxiety, harm avoidance, and reward dependence (P <.05 for all). Women had significantly lower plasma b-endorphin levels at rest (4.2 +/- 3.9 vs 5.0 +/- 2.5 pmol/L for men, P =.005) and at maximal mental stress (6.4 +/- 5.1 vs 7.4 +/- 3.5 pmol/L for men, P <.01). A higher proportion of women than men had marked pain sensitivity to graded heat stimuli applied to skin (hot pain threshold <41 degrees C, 33% vs 10%, P =.001). CONCLUSIONS: Our results reflect sex differences in the affective and discriminative aspects of pain perception and may help explain sex-related differences in clinical presentations.

Activities of Daily Living↗
PubMed2001

Depression, anxiety, and the cardiovascular system: the cardiologist's perspective.

Up to one fifth of patients with cardiovascular disease, including those who have experienced a myocardial infarction, may have concomitant major depression. Studies have suggested that the relative risk of major depression with cardiovascular disease ranges from 1.5 to 4.5. Further information is required to establish a dose-response relationship between depression and coronary artery disease (CAD); however, such a relationship has been shown between anxiety and CAD. Development of a conceptual model of the pathophysiologic actions of stress in CAD will assist in the understanding of this relationship. In patients with angiographic evidence of CAD, the presence of major depressive disorder was the best single predictor of cardiac events during the 12 months following diagnosis. Significantly, 6-month cumulative mortality following diagnosis of myocardial infarction has been shown to be higher in depressed patients than in nondepressed patients. A decrease in heart rate variability may mediate the deleterious effect of depression on post-myocardial infarction prognosis. Other factors such as mental stress and altered platelet function may also predispose depressed patients to a heightened risk of cardiac events. With an increased understanding of the relationship between depression and heightened risk of cardiovascular mortality, it is necessary to assess current overall treatment for cardiac patients.

Anxiety Disorders↗
PubMed2000

Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: A randomized trial. Arterial Disease Multiple Intervention Trial.

CONTEXT: Although niacin increases low levels of high-density lipoprotein cholesterol (HDL-C), which frequently accompany diabetes, current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control; however, this is based on limited clinical data. OBJECTIVE: To determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes. DESIGN AND SETTING: Prospective, randomized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995. PARTICIPANTS: A total of 468 participants, including 125 with diabetes, who had diagnosed peripheral arterial disease. INTERVENTIONS: After an active run-in period, participants were randomly assigned to receive niacin (crystalline nicotinic acid), 3000 mg/d or maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks (12-week active run-in and 48-week double-blind). MAIN OUTCOME MEASURES: Plasma lipoprotein, glucose, hemoglobin A(1c) (HbA(1c)), alanine aminotransferase, and uric acid levels; hypoglycemic drug use; compliance; and adverse events, in patients with diabetes vs without who were receiving niacin vs placebo. RESULTS: Niacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and low-density lipoprotein cholesterol (LDL-C) by 8% and 9%, respectively, in participants with and without diabetes (P<.001 for niacin vs placebo for all). Corresponding changes in participants receiving placebo were increases of 0% and 2% in HDL-C and increases of 7% and 0% in triglycerides, and increases of 1% and 1% in LDL-C. Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P =.04 and P<.001) in participants with and without diabetes, respectively. Levels of HbA(1c) were unchanged from baseline to follow-up in participants with diabetes treated with niacin. In participants with diabetes treated with placebo, HbA(1c) decreased by 0.3% (P =.04 for difference). There were no significant differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo. CONCLUSIONS: Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels. JAMA. 2000;284:1263-1270

Aged↗
PubMed2000

Effective and safe modification of multiple atherosclerotic risk factors in patients with peripheral arterial disease.

BACKGROUND: Patients with peripheral arterial disease (PAD) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors. The Arterial Disease Multiple Intervention Trial (ADMIT) was designed to determine the efficacy, safety, and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD. METHODS: By a 2 x 2 x 2 factorial design, eligible participants (N = 468) were randomly assigned to low-dose warfarin, antioxidant vitamins, and niacin or its corresponding placebo, and followed up for 1 year. All participants were encouraged to use aspirin. Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels. RESULTS: Niacin increased HDL cholesterol levels by 30%, with the majority of effect achieved at a dosage of 500 mg twice daily. Warfarin had an anticoagulant effect. The antioxidant vitamins resulted in a significant increase in vitamin E, C, and beta-carotene plasma levels. Overall, compliance was high and few adverse effects were reported. CONCLUSIONS: ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD.

Aged↗
PubMed1999

Rationale and design of the Arterial Disease Multiple Intervention Trial (ADMIT) pilot study.

The primary objectives of the pilot study were to: (1) evaluate the feasibility of recruiting patients with peripheral arterial disease (PAD); (2) measure the efficacy and safety of high-density lipoprotein (HDL)-raising treatment, low-density lipoprotein (LDL)-lowering therapy, antioxidant therapy, antithrombotic therapy, and their combinations; and (3) assess adherence to a complex multiple drug regimen. Secondary objectives included measurement of the effect of the interventions on prespecified biochemical markers, maintenance of therapy masking (in particular with niacin), and measurement of the intervention's impact on functional status and on quality of life. To date, no secondary prevention trial has been conducted specifically among patients with PAD. Intermittent claudication affects about 0.5% to 1.0% of persons aged >35 years. There is a striking increase in incidence of PAD with age, particularly among those aged >50 years in both sexes, although men are twice as likely as women to develop PAD. The Arterial Disease Multiple Intervention Trial was a double-blind randomized pilot trial of 468 participants with documented PAD. A 2 x 2 x 2 factorial design was used to evaluate the effect of 3 interventions. The pilot incorporated several major novel design features: first, the use of a simple noninvasive method (measurement of ankle brachial index) to identify a population with either symptomatic or asymptomatic PAD; and second, a lipid modifying strategy to increase HDL with nicotinic acid in the intervention group while lowering LDL levels equally with an hydroxymethylglutaryl-coenzyme A reductase inhibitor as needed in the intervention and control group. Two other arms, the antioxidant arm (consisting of beta-carotene and vitamins E and C) and the antithrombotic arm (using warfarin) were also added. Adherence to therapy was measured by pill count, and success in treatment was measured by the proportion of values in target range for HDL, LDL, and the international normalized ratio.

Adult↗
PubMed1999

Comparison of perception of angina pectoris during exercise testing in African-Americans versus Caucasians.

In a sample of 142 patients with positive treadmill test results, we found that African-Americans reported anginal pain during exercise at nearly twice the rate of Caucasians, and had a significantly shorter time to angina. The mechanisms for these race differences remain to be elucidated, but may include underlying physiologic responses, ethnocultural differences, psychological state, socioeconomic differences, and experimenter bias.

Black or African American↗
PubMed1999

Relationship among mental stress-induced ischemia and ischemia during daily life and during exercise: the Psychophysiologic Investigations of Myocardial Ischemia (PIMI) study.

OBJECTIVES: The purposes of this database study were to determine: 1) the relationship between mental stress-induced ischemia and ischemia during daily life and during exercise; 2) whether patients who exhibited daily life ischemia experienced greater hemodynamic and catecholamine responses to mental or physical stress than patients who did not exhibit daily life ischemia, and 3) whether patients who experienced daily life ischemia could be identified on the basis of laboratory-induced ischemia using mental or exercise stress testing. BACKGROUND: The relationships between mental stress-induced ischemia in the laboratory and ischemia during daily life and during exercise are unclear. METHODS: One hundred ninety-six stable patients with documented coronary disease and a positive exercise test underwent mental stress testing and bicycle exercise testing. Radionuclide ventriculography and electrocardiographic (ECG) monitoring were performed during the mental stress and bicycle tests. Patients underwent 48 h of ambulatory ECG monitoring. Hemodynamic and catecholamine responses were obtained during mental stress and bicycle tests. RESULTS: Ischemia (reversible left ventricular dysfunction or ST segment depression > or = 1 mm) developed in 106 of 183 patients (58%) during the mental stress test. There were no significant differences in clinical characteristics of patients with, compared with those without, mental stress-induced ischemia. Patients with mental stress ischemia more often had daily life ischemia than patients without mental stress ischemia, but their exercise tests were similar. Patients with daily life ischemia had higher ejection fraction and cardiac output, and lower systemic vascular resistance during mental stress than patients without daily life ischemia. Blood pressure and catecholamine levels at rest and during the mental stress tests were not different in patients with, compared with those without, daily life ischemia. Patients with daily life ischemia had a higher ejection fraction at rest and at peak bicycle exercise compared with patients without daily life ischemia, but there were no other differences in peak hemodynamic or catecholamine responses to exercise. The presence of ST segment depression during routine daily activities was best predicted by ST segment depression during mental or bicycle exercise stress, although ST segment depression was rare during mental stress. CONCLUSIONS: Patients with daily life ischemia exhibit a heightened generalized response to mental stress. ST segment depression in response to mental or exercise stress is more predictive of ST segment depression during routine daily activities than other laboratory-based ischemic markers. Therapeutic management strategies might therefore focus on patients with these physiologic responses to stress and on whether lessening such responses reduces ischemia.

Activities of Daily Living↗
PubMed1999

Low hot pain threshold predicts shorter time to exercise-induced angina: results from the psychophysiological investigations of myocardial ischemia (PIMI) study.

OBJECTIVES: The purpose of this study was to test whether cutaneous thermal pain thresholds are related to anginal pain perception. BACKGROUND: Few ischemic episodes are associated with angina; symptoms have been related to pain perception thresholds. METHODS: A total of 196 patients with documented coronary artery disease underwent bicycle exercise testing and thermal pain testing. The Marstock test of cutaneous sensory perception was administered at baseline after 30 min of rest on two days and after exercise and mental stress. Resting hot pain thresholds (HPTs) were averaged for the two baseline visits and divided into two groups: 1) average HPT <41 degrees C, and 2) average HPT > or =41 degrees C, to be clearly indicative of abnormal hypersensitivity to noxious heat. RESULTS: Patients with HPT <41 degrees C had significantly shorter time to angina onset on exercise testing than patients with HPT > or =41 degrees C (p < 0.04, log-rank test). Heart rates, systolic blood pressure and rate-pressure product at peak exercise were not different for the two groups. Resting plasma beta-endorphin levels were significantly higher in the HPT <41 degrees C group (5.9+/-3.7 pmol/liter vs. 4.7+/-2.8 pmol/liter, p = 0.02). Using a Cox proportional hazards model, patients with HPT <41 degrees C had an increased risk of angina (p = 0.03, rate ratio = 2.0). These differences persisted after adjustment for age, gender, depression, anxiety and history of diabetes or hypertension (p < 0.01). CONCLUSIONS: Occurrence of angina and timing of angina onset on an exercise test are related to overall hot pain sensory perception. The mechanism of this relationship requires further study.

Adult↗
PubMed1998

Heterogeneity among cardiac ischemic and anginal responses to exercise, mental stress, and daily life.

The objectives of this study were to compare and contrast indicators of ischemia in a well-characterized group of 196 patients with coronary artery disease, documented angiographically or by verified history of myocardial infarction, and a positive exercise test result. Myocardial ischemia occurs frequently in response to everyday stressors in patients with coronary artery disease. The Psychophysiological Interventions in Myocardial Ischemia study provides a unique opportunity to study neuroendocrine and psychological manifestations of ischemia. Patients with exercise-induced ischemia underwent exercise radionuclide ventriculography and electrocardiographic monitoring and 2 laboratory mental stressors (Speech and Stroop) after being withdrawn from cardiac medications. In addition, 48-hour ambulatory electrocardiograms were recorded during routine daily activities. Patients with a history of angina within the past 3 months reported angina during the bicycle or treadmill test with a much higher frequency than patients without such an anginal history (77% vs 26%). Ejection fraction (EF) responses to the Stroop test were abnormal in 48% of patients with an abnormal EF response to the Speech task, versus 17% in patients with a normal EF response (p <0.01). Seventy-six percent of patients had an abnormal EF response to bicycle exercise. Three indicators of ischemia (ST-segment depression, wall motion abnormality, and EF response) were compared during the same laboratory stressor and across different types of stress tests. Presence of the 3 indicators was only moderately associated during exercise, and only weak or nonsignificant associations occurred among the presence of the 3 ischemic markers during mental stress. Occurrence of the same ischemic markers was moderately associated between the 2 mental stress tasks, but few associations were found between the occurrence of the same ischemic marker during exercise and mental stress. There is a marked heterogeneity of responses to psychological and exercise stress testing using electrocardiography, ambulatory electrocardiography, or radionuclide criteria for ischemia during stress. The heterogeneity may be related to differences in the magnitude or types of physiologic responses provoked and to differences in the sensitivity and specificity of the different tests used to identify ischemia.

Aged↗
PubMed1998

Heart rate variability at rest and during mental stress in patients with coronary artery disease: differences in patients with high and low depression scores.

This study tested the hypothesis that coronary artery disease (CAD) patients with high depressed mood scores differ in sympatho-vagal balance during mental stress compared to patients with low depressed mood scores. Using electrocardiographic monitoring, heart variability data from spectral analysis and hemodynamic parameters were obtained prior to and during mental stress from 34 men and 7 women. A public speaking task was used as the mental stressor. Patients were grouped by a median split of their Minnesota Multiphasic Personality Inventory-Depression score. During mental stress, patients with higher depression scores had greater changes in peak heart rate (p < .05) and low frequency to high frequency power ratio (p < 0.05) than patients with lower scores suggesting a shift toward more sympathetic activity during mental stress. These findings may be related to the reported relation between depression and survival risk in patients with CAD.

Journal Article↗
PubMed1997

Association of systolic blood pressure at time of myocardial ischemia with angina pectoris during exercise testing.

In a sample of 306 patients with positive treadmill test results, we found that patients with silent ischemia had a higher systolic blood pressure at onset of ST depression than patients with painful ischemia. We conclude that systolic blood pressure at the time of ischemia influences the experience of angina during exercise in a manner consistent with acute activation of baroreceptors and resulting antinociception.

Angina Pectoris↗
PubMed1997

Associations of ankle-brachial index with clinical coronary heart disease, stroke and preclinical carotid and popliteal atherosclerosis: the Atherosclerosis Risk in Communities (ARIC) Study.

The resting ankle-brachial index (ABI) is a non-invasive method to assess the patency of the lower extremity arterial system and to screen for the presence of peripheral occlusive arterial disease. To determine how the ABI is associated with clinical coronary heart disease (CHD), stroke, preclinical carotid plaque and far wall intimal-medial thickness (IMT) of the carotid and popliteal arteries, we conducted analyses in 15 106 middle-aged adults from the baseline examination (1987-1989) of the Atherosclerosis Risk in Communities (ARIC) Study. The prevalence of clinical CHD, stroke/transient ischemic attack (TIA) and preclinical carotid plaque increased with decreasing ABI levels, particularly at those of < 0.90. Individuals with ABI < 0.90 were twice as likely to have prevalent CHD as those with ABI > 0.90 (age-adjusted odds ratio (OR) ranging from 2.2 (95% CI: 1.0-5.1) in African-American men to 3.3 (95% CI: 2.1-5.0) in white men). Men with ABI < 0.90 were more than four times as likely to have stroke/TIA as those with ABI > 0.90 (age-adjusted OR: 4.2 (95% CI: 1.8-9.5) in African-American men and 4.9 (95% CI: 2.6-9.0) in white men). In women the association was weaker and not statistically significant. Among those free of clinical cardiovascular disease, individuals with ABI < or = 0.90 had statistically significantly higher prevalence of preclinical carotid plaque compared to those with ABI > 0.90 (age-adjusted ORs ranging from 1.5 (95% CI: 1.0-1.9) in white women to 2.6 (95% CI: 1.0-6.6) in african-american men). The ABI was also inversely associated with far wall IMT of the carotid arteries (in both men and women) and the popliteal arteries (in men only). The associations of ABI with clinical CHD, stroke, preclinical carotid plaque and IMT of the carotid and popliteal arteries were attenuated and often not statistically significant after further adjustment for LDL cholesterol, cigarette smoking, hypertension and diabetes. These data demonstrate that low ABI levels, particularly those of < 0.90, are indicative of generalized atherosclerosis.

Ankle↗
PubMed1997

The relationship between resting systolic blood pressure and cutaneous pain perception in cardiac patients with angina pectoris and controls.

In order to determine the influence of resting systolic blood pressure and stable angina on cutaneous pain perception, we studied 19 male cardiac patients with stable angina and 16 male controls. Pain perception was measured using a suprathreshold evaluation of pain intensity and pain unpleasantness to a series of thermal stimuli. We found that men with higher resting blood pressure had a decrease in the perception of pain intensity and pain unpleasantness. Similarly, we found that patients with stable angina perceived pain as less intense and unpleasant than controls. These differences in pain perception may be associated with different pain mechanisms: in the case of blood pressure, differences in opioid activity and baroreceptor-regulated pain systems; in the case of stable angina, patients may adapt to continued experiences of pain, altering internal frames of reference.

Analysis of Variance↗
PubMed1996

Left ventricular, peripheral vascular, and neurohumoral responses to mental stress in normal middle-aged men and women. Reference Group for the Psychophysiological Investigations of Myocardial Ischemia (PIMI) Study.

BACKGROUND: The normal cardiovascular response to mental stress in middle-aged and older people has not been well characterized. METHODS AND RESULTS: We studied 29 individuals 45 to 73 years old (15 women, 14 men) who had no coronary risk factors, no history of coronary artery disease, and a negative exercise test. Left ventricular (LV) volumes and global and regional function were assessed by radionuclide ventriculography at rest and during two 5-minute standardized mental stress tasks (simulated public speaking and the Stroop Color-Word Test), administered in random order. A substantial sympathetic response occurred with both mental stress tests, characterized by increases in blood pressure, heart rate, rate-pressure product, cardiac index, and stroke work index and rises in plasma levels of epinephrine and norepinephrine but not beta-endorphin or cortisol. Despite this sympathetic response, LV volume increased and ejection fraction (EF) decreased secondary to an increase in afterload. The change in EF during mental stress-varied among individuals but was associated positively with changes in LV contractility and negatively with baseline EF and changes in afterload. EF decreased > 5% during mental stress in 12 individuals and > 8% in 5; 3 developed regional wall motion abnormalities. CONCLUSIONS: Mental stress in the laboratory results in a substantial sympathetic response in normal middle-aged and older men and women, but EF commonly falls because of a concomitant rise in afterload. These results provide essential age- and sex-matched reference data for studies of mental stress-induced ischemia in patients with coronary artery disease.

Aged↗
PubMed1996

Ischemic, hemodynamic, and neurohormonal responses to mental and exercise stress. Experience from the Psychophysiological Investigations of Myocardial Ischemia Study (PIMI).

BACKGROUND: The pathophysiology of mental stress-induced myocardial ischemia, which occurs at lower heart rates than during physical stress, is not well understood. METHODS AND RESULTS: The Psychophysiological Investigations of Myocardial Ischemia Study (PIMI) evaluated the physiological and neuroendocrine functioning in unmedicated patients with stable coronary artery disease and exercise-induced ischemia. Hemodynamic and neurohormonal responses to bicycle exercise, public speaking, and the Stroop test were measured by radionuclide ventriculography, ECG, and blood pressure and catecholamine monitoring. With mental stress, there were increases in heart rate, systolic blood pressure, cardiac output, and systemic vascular resistance that were correlated with increases in plasma epinephrine. During exercise, systemic vascular resistance fell, and there was no relationship between the hemodynamic changes and epinephrine levels. The fall in ejection fraction was greater with mental stress than exercise. During mental stress, the changes in ejection fraction were inversely correlated with the changes in systemic vascular resistance. Evidence for myocardial ischemia was present in 92% of patients during bicycle exercise and in 58% of patients during mental stress. Greater increases in plasma epinephrine and norepinephrine occurred with ischemia during exercise, and greater increases in systemic vascular resistance occurred with ischemia during mental stress. CONCLUSIONS: Mental stress-induced myocardial ischemia is associated with a significant increase in systemic vascular resistance and a relatively minor increase in heart rate and rate-pressure product compared with ischemia induced by exercise. These hemodynamic responses to mental stress can be mediated by the adrenal secretion of epinephrine. The pathophysiological mechanism involved are important in the understanding of the etiology of myocardial ischemia and perhaps in the selection of appropriate anti-ischemic therapy.

Adult↗