Biomedical subjects
Publications and source records attributed to L T Clark.
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Plasma high density lipoprotein cholesterol (HDL-C) concentrations are higher in African American men than in white men, but the mechanism(s) responsible for this ethnic difference has not been elucidated. This study examined the relationship between hepatic lipase activity, plasma HDL-C concentrations, and a hepatic lipase polymorphism (-514T) in African American and white American men. Consistent with previous reports, plasma HDL-C concentrations were significantly higher in African American men than in white American men. Mean post-heparin plasma hepatic lipase activity was significantly lower in African American than in white American men (27 +/- 12 vs. 44 +/- 17 mmol x h(-1) x l(-1), P < 0.001). The -514T hepatic lipase allele was associated with low hepatic lipase activity in both populations, and was 3-fold more common among African Americans than white Americans. Taken together, these data suggest that genetic differences in hepatic lipase activity contribute to the differences in plasma HDL-C concentrations between African American men and white American men.
The -514 polymorphism in the hepatic lipase gene (LIPC) is associated with decreased hepatic lipase activity. In the present study, the interaction between body mass index (BMI), the -514 polymorphism, and hepatic lipase activity was examined in 118 white men and in 51 African American men. BMI was significantly positively correlated with hepatic lipase activity in both populations. BMI was similar in men with genetic differences in hepatic lipase activity, indicating that high hepatic lipase activity did not cause increased BMI. The data therefore suggest that high BMI leads to increased hepatic lipase activity. The actions of BMI and the -514 polymorphism on hepatic lipase activity appear to be additive and independent, rather than synergistic. This finding indicates that hepatic lipase activity is a multifactorial trait, determined in part by polymorphism within the LIPC gene as well as by factors that influence BMI.
We have shown previously that a hepatic lipase allele (designated -514T) is common among African Americans and contributes to low hepatic lipase activity in this population. To identify other hepatic lipase alleles associated with low hepatic lipase activity in this population, the coding region and intron-exon boundaries of the hepatic lipase gene were sequenced in 20 African American men with low hepatic lipase activity. Two polymorphisms (N193S and L334F) were associated with low post-heparin plasma hepatic lipase activity and were much more common in African Americans than in whites. This finding, together with our previous data on the -514T allele, indicates that at least three different hepatic lipase polymorphisms associated with low hepatic lipase activity are common among African Americans. Analysis of hepatic lipase haplotypes revealed that 97% of African Americans have at least one hepatic lipase allele that is associated with low hepatic lipase activity.
Physicians and other health care professionals play an important role in reducing the delay to treatment in patients who have an evolving acute myocardial infarction. A multidisciplinary working group has been convened by the National Heart Attack Alert Program (which is coordinated by the National Heart, Lung, and Blood Institute of the National Institutes of Health) to address this concern. The working group's recommendations target specific groups of patients: those who are known to have coronary heart disease, atherosclerotic disease of the aorta or peripheral arteries, or cerebrovascular disease. The risk for acute myocardial infarction or death in such patients is five to seven times greater than that in the general population. The working group recommends that these high-risk patients be clearly informed about symptoms that they might have during a coronary occlusion, steps that they should take, the importance of contacting emergency medical services, the need to report to an appropriate facility quickly, treatment options that are available if they present early, and rewards of early treatment in terms of improved quality of life. These instructions should be reviewed frequently and reinforced with appropriate written material, and patients should be encouraged to have a plan and to rehearse it periodically. Because of the important role of the bystander in increasing or decreasing delay to treatment, family members and significant others should be included in all instruction. Finally, physicians' offices and clinics should devise systems to quickly assess patients who telephone or present with symptoms of a possible acute myocardial infarction.
Pulsus alternans is usually found in patients with reduced systolic ventricular function. We describe a patient with recurrent pulmonary edema, hypertension, bilateral renal artery stenosis, but with normal systolic function. Pulsus alternans was demonstrated in both pulmonary artery, right ventricle, and left ventricle pressures. After successful renal artery revascularization, the pulsus alternans disappeared. This case illustrates that pulsus alternans can be present with diastolic dysfunction of the left ventricle in the absence of systolic dysfunction.
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PURPOSE: To evaluate the impact of a unique school-based program of exercise, health education, and behavior modification on health knowledge, health behaviors, coronary risk factors, and cardiovascular fitness in minority adolescents. METHODS: A total of 346 students from an inner-city public high school participated in health promotion intervention or regular physical education volleyball classes. Subjects were African-American (47%), Asian-American (9%), Hispanic (21%), white (3%), and other (19%). The health promotion curriculum consisted of 11 weeks of daily circuit training exercise and health lecture-discussions. RESULTS: The groups were similar in age, height, weight, ethnicity, and socioeconomic status. Following intervention both boys (P < .001) and girls (P < .006) significantly improved health knowledge test scores. Significant benefits for girls included improved dietary habits (P < .05), reduced cholesterol (P < .004), and higher estimated V(O2)max (P < .0001). There were no other significant changes in boys. CONCLUSIONS: The results suggest that a school-based health promotion program of exercise and health lecture-discussion is beneficial for multiethnic, inner-city adolescents, especially females.
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The United States has a shortage of physicians from underrepresented minorities. Under-representation of ethnic minority academic faculty is due to multiple factors, including an inadequate number of minority medical school graduates, indebtedness of minority postgraduate trainees, lack of awareness of opportunities in academic medical centers, lack of mentors, a shortage of role models, and environmental factors. Over recent years, the government, private industry, and some universities and medical schools have made efforts to remedy this situation. The problems, however, are complex and difficult to solve. There is a need to increase the pool of underrepresented minority students interested in careers in medicine; to promote medical student, graduate student, and house staff awareness of career opportunities in academics; to provide resources that enable students, house staff, and fellows to develop the skills necessary to succeed and survive in the academic arena; and to offer ongoing support for career development of junior faculty. A number of programs exist for attracting more minorities to academic medicine, but obtaining information on them is often difficult. The development of a centralized resource center where program information is readily available should be a priority. An effort to coordinate activities of existing programs by the Institute of Medicine and/or the Association of American Medical Colleges (AAMC) is needed. A target goal should be developed for increasing minorities in graduate medical education and academic medicine similar to the AAMC's Project 3000 by 2000.
Although the mortality rate from coronary heart disease (CHD) has declined by almost 50% during the past 25 years, CHD remains the leading cause of death in the United States and is responsible for more than 500,000 deaths annually. The underlying cause of CHD is coronary atherosclerosis. Although the intact intima is highly resistant to thrombus formation, when injury occurs, even superficial, a sequence of reactions is initiated--platelet aggregation, macrophage accumulation, intimal smooth muscle proliferation, fibrous tissue proliferation, and lipid accumulation--that result in the development of obstructive atheroma. Repeat intimal injury and cycling of this process lead to continued progression of the atheroma and coronary artery occlusion. Unstable angina and acute myocardial infarction appear to result from rupture of an atherosclerotic plaque, hemorrhage into the plaque, and luminal thrombosis. The cause of plaque rupture is unknown and may result from normal hemodynamic forces when the fibrous cap of an atheroma has become severely attenuated and fragile. Based on the pathogenesis of chronic atherosclerosis and acute rapid atheroma progression, several therapeutic options become evident. These include antiplatelet, anticoagulant, and thrombolytic therapies, as well as the possibility of arrest and reversal of atherosclerosis in some patients.
In this study, we analyzed the duration and determinants of prehospital delay in a group of inner-city patients hospitalized with suspected myocardial infarction. The average prehospital delay was 11.9 +/- 25.1 hours. Mean and median delays were similar for males (mean: 10.9 +/- 24.2 hours; median: 2.8 hours) and females (mean: 12.7 +/- 25.7 hours; median: 3.5 hours), but were longer for blacks (mean: 13.1 +/- 27.5 hours, P < .001; median: 3 hours, P = .06) and Hispanics (mean: 12.4 +/- 19.3 hours, P < .01; median: 4 hours, P = .07) than for whites (mean: 3.3 +/- 2.9 hours; median: 2 hours). Most of the observed delay was due to the time it took for patients to decide to seek medical care following onset of symptoms. Patients were more likely to arrive at the hospital within 4 hours if they thought their symptoms might be a heart attack (79% versus 41%, P < .01), if they believed that coronary heart disease was preventable (68% versus 42%, P < .01), and if they took an ambulance to the hospital (68% versus 47%, P < .01). The factor most strongly associated with early hospital arrival was the patient's belief that the symptoms might represent a heart attack; these patients were five times more likely to get to the hospital within 4 hours than others, independent of other factors. Interventions designed to decrease prehospital delay must focus not only on improving knowledge of symptoms, but also on identifying high-risk patients and increasing patient awareness of the benefits of early response and treatment.
Approximately 60 million people in the United States have hypertension. More than half are either untreated or treated without blood pressure control, despite the well-known risks of hypertension and the established benefits of treatment. The major reason for inadequate control of hypertension is poor adherence to treatment. Approximately 50% of patients with hypertension fail to keep follow-up appointments, and only 60% take their medications as prescribed. Barriers to effective therapeutic adherence include poor doctor-patient communication, cost of antihypertensive therapy, and side effects of the drugs. To increase control of hypertension, compliance with therapy must be improved. Physicians and patients must be mutually committed to achieving control of blood pressure. Physicians should communicate instructions clearly and prescribe therapies that are effective, affordable, and have minimal or no adverse effects on patient quality of life or overall cardiac risk profile. The needs of special hypertensive populations (i.e., elderly, black, and young patients) must also be recognized and addressed. Patients must follow recommendations and alert their physicians to any problems with their medications--particularly those relating to side effects and cost. When selecting drug therapy it should be noted that older patients are sensitive to volume depletion and sympathetic inhibition. In this group of patients, initial drug doses should be low and increments smaller and more gradual than in younger patients. Black patients with hypertension show an accentuated response to diuretics and blunted responses to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors as monotherapy. However, when used with a diuretic, there are no racial differences in the blood pressure lowering effects of beta-blockers and ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)
The clinical features of 304 patients with acute myocardial infarction with and without hypertension were studied retrospectively. This inner city population consisted of 172 (57%) males and 132 (43%) females; 155 (51%) patients were black, 88 (29%) Hispanic, and 61 (20%) white by self-identification. Hypertension (greater than or equal to 160/95 mmHg) was present on admission in 46% (139) of patients. Typical ischaemic chest pain was the most common presenting symptom and occurred with a similar frequency in patients with and without hypertension. However, the group with hypertension consisted of proportionately more females than males, more frequently had previously diagnosed hypertension and congestive heart failure, and more often presented with shortness of breath and pulmonary oedema. The racial distribution, mean ages, prevalence of angina, previous myocardial infarction, diabetes, smoking, family history of cardiovascular disease, type of myocardial infarction, peak creatinine phosphokinase, plasma cholesterol, and mortality rates were similar in both groups. Thus, female sex, history of hypertension, history of congestive heart failure, and pulmonary oedema characterised patients with compared to those without hypertension. These findings suggest that the higher mortality rate observed in hypertensives during follow-up after myocardial infarction may be due, at least in part, to more severe underlying left ventricular dysfunction.
Despite recent declines in mortality from coronary heart disease (CHD), it remains the major cause of death in the United States for blacks and whites. Although the prevalence of the ischemic syndromes in blacks and whites is similar, cardiac mortality and sudden cardiac death rate are higher in blacks. Recent attempts to explain the excess mortality in blacks have focused on barriers to health care and on sociocultural differences in perceptions of and responses to symptoms of CHD. However, the anatomic substrates of ischemia and sudden cardiac death are also different in blacks and whites. Obstructive coronary artery disease tends to be more severe in whites, while blacks have a greater prevalence of hypertensive heart disease. A body of evidence has recently emerged showing that the presence of left ventricular hypertrophy (LVH) is an important, potent predictor for subsequent cardiac death and that the mortality risk of LVH may be particularly high when underlying coronary disease is present. The greater prevalence and severity of hypertension and LVH in blacks may explain the higher cardiac mortality in blacks, even in the presence of less severe coronary disease. The reason why mortality risk is increased in the presence of LVH has not been established. Evidence suggests that it may be due to the increased predisposition to malignant arrhythmias and the increased frequency of potentially lethal silent ischemic events that occur in hypertensive individuals, particularly those with LVH.
The development of a novel model of human alcoholism has involved the presentation of a 30% alcohol solution to Sprague-Dawley rats via a syringe-feeding needle apparatus. With twice daily intermittent drinking, rats consumed an equivalent of 7-8 g/kg body weight of alcohol, which represented 25% of total daily caloric intake. Alcohol was absorbed rapidly, as significant circulating concentrations were observed within 15 min of gavage, eventually peaking at approximately 200 mg% 1 h later. Hemodynamic recordings in the conscious state after a 10-week drinking program indicated a normotensive blood pressure at peak blood alcohol levels, yet a hypertensive response 24 h after the final drink at a time when blood alcohol was not detected. Alcoholic rats continued to gain weight in parallel with controls fed ad libitum throughout the study, and changes in cardiac size and indices of contractility were not affected by 10 weeks of intermittent drinking. Additionally, no histological evidence of cardiac muscle damage was observed in alcoholic animals. Our animal model closely resembles the clinical situation in terms of the pattern of alcohol consumption, circulating concentrations of alcohol and the percentage of caloric intake in the form of alcohol. The hemodynamic changes observed support the hypothesis that alcoholic hypertension may be a manifestation of withdrawal, as opposed to any direct pressor effect of alcohol itself.
The clinical features of an inner-city population of 304 patients presenting with acute myocardial infarction (MI) with and without typical chest pain, were studied retrospectively. This population consisted of 172 men and 132 women; 155 (51%) were black, 88 (29%) hispanic, and 61 (20%) white, by self-identification. Typical ischemic chest pain was the presenting symptom in 85% (258); 15% (46) presented with nonchest symptoms, most frequently shortness of breath, abdominal pain, and dizziness. But the frequency of such nonchest symptoms was similar in both groups. When patients were grouped by the presence or absence of chest pain, the proportions of those without chest pain were significantly higher for blacks (22.7%) than hispanics (9.1%, P = 0.001) or whites (4.9%, P less than 0.01). Patients without chest pain also had higher admission systolic (P less than 0.01) and diastolic (P less than 0.01) blood pressures and more frequent histories of congestive heart failure (P less than 0.05), and more often presented with pulmonary edema (P = 0.001) than those with chest pain. Both groups were similar in age, sex, history of hypertension, and presence of hypertension on admission, defined as greater than or equal to 160/95 mmHg, prevalence of diabetes, history of smoking, previous MI, type of MI, history of angina, and mortality rates. Patients without chest pain were characterized by black race, history of congestive heart failure, elevated blood pressure and pulmonary edema than those with typical ischemic chest pain. Thus significant delays in the diagnosis and treatment of this important clinical entity may be reduced by alerting clinicians to these features and by educating selected patient groups.
Alcohol use is associated with an increased prevalence of hypertension although the responsible mechanisms and hemodynamic correlates have not been well-defined. Disorders of electrolyte and water metabolism with resultant retention of sodium and water are common in alcoholics. However, although volume relates to cardiac output, and cardiac output to blood pressure, plasma volume expansion does not appear to be important in the development of the hypertension associated with chronic alcoholic use. Most available evidence suggests that the primary underlying mechanism is increased vascular resistance. Chronic alcohol administration may produce an increased accumulation of cytoplasmic calcium in vascular smooth muscle with vascular hyperreactivity, vasoconstriction, and increased peripheral resistance. Although precise mechanisms have not been elucidated, this may result from (1) a direct effect of alcohol on plasma membrane permeability, sodium transport, and Na+/Ca2+ exchange, and/or (2) impaired calcium transport due to a secondary abnormality such as magnesium depletion, which is present in alcoholics.