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C D Furberg

Publications and source records attributed to C D Furberg.

At least 19 recordsLinked to original sources

Isolated systolic hypertension and subclinical cardiovascular disease in the elderly. Initial findings from the Cardiovascular Health Study.

OBJECTIVE: To assess the association between isolated systolic hypertension (ISH) and subclinical disease in adults aged 65 years and above. DESIGN: Medicare eligibility lists were used to obtain a representative sample of 5201 community-dwelling elderly persons for the Cardiovascular Health Study, a National Heart, Lung, and Blood Institute--sponsored cohort study of risk factors for coronary heart disease and stroke. In this cross-sectional analysis of baseline data, we excluded 3012 participants who were receiving antihypertensive medications, had clinical cardiovascular disease, or had a diastolic blood pressure of at least 90 mm Hg. MAIN OUTCOME MEASURES: For electrocardiogram: myocardial infarction, left ventricular hypertrophy, and left ventricular mass as measures of myocardial damage and strain; for echocardiography: left ventricular mass, fractional shortening, and Doppler flow velocities as measures of cardiac systolic and diastolic function; and for carotid sonography: carotid arterial intima-media thickness as a measure of atherosclerosis. RESULTS: Among the 2189 men and women in this analysis, 195 (9%) had ISH (systolic blood pressure, greater than or equal to 160 mm Hg) and 596 (23%) had borderline ISH (systolic blood pressure, 140 to 159 mm Hg). Systolic blood pressure was associated with myocardial infarction by electrocardiogram (P = .02). Borderline and definite ISH were strongly associated with left ventricular mass (P less than .001). While there was little association with cardiac systolic function, borderline and definite ISH were associated with cardiac diastolic function (P less than .001). Isolated systolic hypertension was also strongly associated with increased intima-media thickness of the carotid artery (P less than .001). CONCLUSIONS: While cohort analyses of future repeated measures will provide a better assessment of risk, both borderline and definite ISH were strongly related to a variety of measures of subclinical disease in elderly men and women.

Aged

Major electrocardiographic abnormalities in persons aged 65 years and older (the Cardiovascular Health Study). Cardiovascular Health Study Collaborative Research Group.

Electrocardiographic abnormalities are often found in older patients, but their prevalence in free-living elderly populations is not well-defined. In addition, the clinical significance of many of these abnormalities is uncertain. The prevalence of major electrocardiographic abnormalities was determined in 5,150 adults aged greater than or equal to 65 years from the Cardiovascular Health Study--a study of risk factors for stroke and coronary heart disease in the elderly. Ventricular conduction defects, major Q/QS waves, left ventricular hypertrophy, isolated major ST-T-wave abnormalities, atrial fibrillation and first-degree atrioventricular block were collectively categorized as major electrocardiographic abnormalities. Prevalence of any major electrocardiographic abnormality was 29% in the entire cohort, 19% among 2,413 participants who reported no history of coronary artery disease or systemic hypertension, and 37% among 2,737 participants with a history of coronary artery disease or hypertension. Prevalence of major electrocardiographic abnormalities was higher in men than in women regardless of history, and tended to increase with age. Major Q/QS waves were found in 5.2%, and more than half were in those who did not report a previous myocardial infarction. Major electrocardiographic abnormalities are common in elderly men and women irrespective of the history of heart disease.

Age Factors

Eligibility for cholesterol referral in community-dwelling older adults. The Cardiovascular Health Study.

OBJECTIVES: To assess the proportion of community-dwelling adults aged 65 years or older who are eligible for referral for lipoprotein analysis and intervention according to the National Cholesterol Education Program (NCEP) guidelines. DESIGN: Cross-sectional study based on examinations and questionnaires collected in 1989 and 1990. SETTING: Four communities in the U.S. in the Cardiovascular Health Study (CHS), a study of risk factors for heart disease and stroke in older adults. PARTICIPANTS: A sample of 4810 men and women ages 65 to 100 randomly selected and recruited from Health Care Financing Administration Medicare eligibility lists for the four communities; not institutionalized, not wheelchair-bound, not currently receiving therapy for cancer, not currently taking lipid-lowering medications, and not having eaten in the preceding 9 hours. MEASUREMENTS: Total cholesterol and lipoprotein analysis measured in all participants. RESULTS: Total cholesterol levels were less than 5.17 mmol/L (200 mg/dL) in 37% of participants, 5.17 to 6.19 mmol/L (200 to 239 mg/dL) in 39%, and 6.20 mmol/L (240 mg/dL) or greater in 24%. Compared with their counterparts, older participants, especially those over 80 years of age, were more likely to have levels below 5.17 mmol/L, as were men, nonwhites, and those with coronary heart disease or two or more coronary heart disease risk factors (P less than 0.008 for all values). Based on this screening measurement, 2174 participants were eligible for lipoprotein analysis, 80% were eligible for dietary or drug therapy using NCEP guidelines. Overall, 46% of CHS participants were eligible for lipoprotein analysis and 36% for intervention by NCEP guidelines, based on a single cholesterol measurement. CONCLUSION: A substantial proportion of older adults in this community sample were eligible for lipoprotein analysis and intervention. Prospective studies of elderly persons are needed to determine the risk for incident coronary heart disease according to NCEP classifications and the benefits of lipid-lowering treatments in persons in this age group so that intervention strategies may best be targeted to an appropriately high-risk group.

Age Factors

Pravastatin, lipids, and atherosclerosis in the carotid arteries: design features of a clinical trial with carotid atherosclerosis outcome.

The Pravastatin, Lipids, and Atherosclerosis in the Carotids trial (PLAC-II) was initiated in 1987 and is the first double-masked randomized clinical trial with progression of early extracranial carotid atherosclerosis as an outcome variable. The trial will compare a lipid-lowering agent (pravastatin, a hydroxymethylglutaryl CoA reductase inhibitor) with placebo for ability to retard the rate of progression of extracranial carotid atherosclerosis over 3 years. Inclusion criteria consisted of prevalent coronary artery disease, moderately elevated low-density lipoprotein (LDL) cholesterol (between the 60th and 90th percentiles), and the presence of at least one extracranial carotid artery atherosclerotic plaque that had an intimal-medial thickness (IMT) > or = 1.3 mm as visualized by B-mode ultrasound. Of approximately 650 patients who qualified on the basis of coronary disease and elevated LDL cholesterol, 55% were excluded because of B-mode criteria. One hundred and fifty-one males and females 50-75 years of age were recruited. Random allocation produced placebo-treated and test-treated groups that were similar for baseline historical data, physical findings, laboratory tests, lipid values, and B-mode characteristics. Baseline concentrations of plasma total cholesterol, LDL cholesterol, and high-density lipoprotein (HDL) cholesterol were 234, 166, and 41 mg/dl, respectively. Baseline plasma concentration of triglyceride was 170 mg/dl. Despite selection of participants whose arteries, overall, were suitable for the trial, individual segments in some participants could not be visualized. Ninety-seven percent of the individual carotid artery segments were visualized in the common carotid, 88% in the bifurcation, and 63% in the internal carotid artery. Far walls were slightly more often visualized than near walls, and nonvisualization was most common for the near wall of the internal carotid. Nonvisualized segments were comparable between both treatment groups. The distribution of arterial walls with qualifying plaque of > or = 1.3 mm IMT was similar for the two groups, and the two groups were also comparable for the primary outcome determinant, mean maximum IMT (mean of maximum of all visualizable sites, 1.32 mm for each treatment group). There are special problems related to recruitment and evaluation of patients for a clinical trial such as this, but the atherosclerosis outcome measurement markedly enhances power and compensates for difficulty in recruitment.

Aged

Quality of life with three antihypertensive treatments. Cilazapril, atenolol, nifedipine.

A multicenter, randomized double-blind study of 6 months' duration was performed in 540 patients (average age 54 years, 57% male) with mild-to-moderate essential hypertension to determine the relative effects on quality of life of cilazapril, atenolol, and nifedipine retard. Quality of life was assessed by using both a self-administered and an interviewer-administered questionnaire; the assessment included a complaint score (symptoms checklist), Health Status Index, assessment of work satisfaction, Psychological General Well-being Index, Profile of Mood States subscales, and life satisfaction assessment. Psychomotor function was measured by the Reitan Trail Making test B. At the end of the trial, diastolic blood pressure had fallen by an average of 15 mm Hg in all three groups, but significantly (p = 0.01) more patients taking cilazapril required the addition of a diuretic (36%) compared with those taking atenolol (25%) or nifedipine retard (24%). No significant differences in quality of life were observed between cilazapril and atenolol during the trial. Symptomatic complaints increased on nifedipine retard (p = 0.02) and contributed to a higher discontinuation rate (21% discontinued treatment compared with 13% and 14% taking atenolol and cilazapril, respectively, p = 0.04). However, a possible improvement in the fatigue subscale (p = 0.04) was also observed on nifedipine retard. The 95% confidence intervals showed that none of the drugs in this trial produced an effect equivalent to that previously reported between captopril and methyldopa in the Psychological General Well Being Index or between captopril and methyldopa or propranolol in Trail Making test B.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors

Reproducibility of noninvasive ultrasonic measurement of carotid atherosclerosis. The Asymptomatic Carotid Artery Plaque Study.

BACKGROUND AND PURPOSE: To determine the effect of a lipid-lowering agent and/or a low-dose antithrombotic agent on the progression of early-stage carotid atherosclerosis, noninvasive B-mode ultrasound was used to measure intimal-medial thickness in asymptomatic individuals with moderately elevated lipids as part of the ongoing multicenter Asymptomatic Carotid Artery Plaque Study. METHODS: Uniform ultrasonic scanning and reading protocols were implemented to obtain maximum intimal-medial thickness measurements in 12 standard segments in patients having a small to moderate wall thickness (1.5-3.5 mm) in at least one of the carotid arteries. Paired B-mode image recordings on 858 patients, performed 1 month apart and read at a core laboratory (each pair by the same reader), determined both within-sonographer (W, n = 405) and between-sonographer (B, n = 453) reproducibility. RESULTS: The primary end point (mean +/- SD), defined in each individual as the mean value of the 12 maximum intimal-medial thickness measurements, was 1.31 +/- 0.21 mm (W) and 1.32 +/- 0.22 (B) at the time of the second examination. The mean difference in the primary end point (exam 2-exam 1) was -0.01 +/- 0.13 mm (W) and 0.00 +/- 0.15 mm (B). The Pearson correlation coefficients were 0.79 (W) and 0.75 (B). In 90% of the patients, the absolute difference in the primary end point was less than 0.22 mm (W) and less than 0.24 mm (B). Variability of the secondary end point, defined as the single largest intimal-medial thickness measurement in a patient, was between three and four times larger than the variability for the primary end point. Differences in sonographer performance between clinical centers were very small. CONCLUSIONS: The results demonstrate that standardized noninvasive ultrasonic techniques yield highly reproducible measures of carotid intimal-medial thickness, which can serve as a measure of carotid atherosclerosis in clinical trials that monitor small rates of lesion progression.

Adult

Lack of age-related differences in the clinical presentation of digoxin toxicity.

BACKGROUND: Digoxin toxicity occurs most commonly among the elderly. While the clinical syndrome of digoxin toxicity is well understood, how toxic manifestations change with age is not known. METHODS: We performed secondary analysis of data from a postmarketing surveillance study of patients with life-threatening digoxin toxicity treated with digoxin antibody therapy. Patients receiving long-term maintenance digoxin therapy and aged 55 years or older were divided into four age groups: 55 to 64, 65 to 74, 75 to 84, and 85 years and older (n = 45, 167, 183, and 83, respectively) and compared with regard to presenting manifestations, digoxin dosing, serum potassium and digoxin levels, and renal function. RESULTS: The prevalence of high-degree atrioventricular block showed an increasing but nonsignificant trend with age (40%, 40%, 42%, and 47%, respectively). Age-related trends in high-degree atrioventricular block were stronger among men than women and even stronger among men with underlying cardiac ischemia. The proportion of subjects with nausea/vomiting as a toxic manifestation did not consistently change with age (42%, 48%, 48%, and 46%, respectively). There were no age-related differences in degree of renal impairment or maintenance dose, but maintenance dose decreased with increasing renal impairment. CONCLUSIONS: Among patients with life-threatening digoxin toxicity, there is no age-related difference in clinical presentation.

Age Factors

Digoxin Immune Fab therapy in the management of digitalis intoxication: safety and efficacy results of an observational surveillance study.

An observational surveillance study was conducted to monitor the safety and effectiveness of treatment with Digoxin Immune Fab (Ovine) (Digibind) in patients with digitalis intoxication. Before April 1986, a relatively limited number of patients received treatment with digoxin-specific Fab fragments through a multicenter clinical trial. Beginning with commercial availability in July 1986, this study sought additional, voluntarily reported clinical data pertaining to treatment through a 3 week follow-up. The study included 717 adults who received Digoxin Immune Fab (Ovine). Most patients were greater than or equal to 70 years old and developed toxicity during maintenance dosing with digoxin. Fifty percent of patients were reported to have a complete response to treatment, 24% a partial response and 12% no response. The response for 14% of patients was not reported or reported as uncertain. Six patients (0.8%, 95% confidence interval 0.3% to 1.8%) had an allergic reaction to digoxin-specific antibody fragments. Three of the six had a history of allergy to antibiotic drugs. Twenty patients (2.8%, 95% confidence interval 1.7% to 4.3%) developed recrudescent toxicity. Risk of recrudescent toxicity increased sixfold when less than 50% of the estimated dose of antibody was administered. A total of 215 patients experienced posttreatment adverse events. The events for 163 patients (76%) were judged to result from manifestations of underlying disease and thus considered unrelated to Fab treatment. Digoxin-specific antibody fragments were generally well tolerated and clinically effective in patients judged by treating physicians to have potentially life-threatening digitalis intoxication.

Adolescent

Organizing multicenter trials: lessons from cardiovascular prevention trials.

Careful and thorough planning are essential aspects of a clinical trial that can make the difference and lead to a more successful trial. The value of feasibility studies should be recognized. The use of surrogate endpoints has justifiably come under increased scrutiny. The many complex issues of implementation demand experienced trial investigators. An openness to learn from lessons in previous trials is essential.

Cardiovascular Diseases

The Cardiovascular Health Study: design and rationale.

The Cardiovascular Health Study (CHS) is a population-based, longitudinal study of coronary heart disease and stroke in adults aged 65 years and older. The main objective of the study is to identify factors related to the onset and course of coronary heart disease and stroke. CHS is designed to determine the importance of conventional cardiovascular disease (CVD) risk factors in older adults, and to identify new risk factors in this age group, especially those that may be protective and modifiable. The study design called for enrollment of 1250 men and women in each of four communities: Forsyth County, North Carolina; Sacramento County, California; Washington County, Maryland; and Pittsburgh, Pennsylvania. Eligible participants were sampled from Medicare eligibility lists in each area. Extensive physical and laboratory evaluations were performed at baseline to identify the presence and severity of CVD risk factors such as hypertension, hypercholesterolemia and glucose intolerance; subclinical disease such as carotid artery atherosclerosis, left ventricular enlargement, and transient ischemia; and clinically overt CVD. These examinations in CHS permit evaluation of CVD risk factors in older adults, particularly in groups previously under-represented in epidemiologic studies, such as women and the very old. The first of two examination cycles began in June 1989. A second comprehensive examination will be repeated three years later. Periodic interim contacts are scheduled to ascertain and verify the incidence of CVD events, the frequency of recurrent events, and the sequellae of CVD.

Aged

Propranolol-induced lipid changes and their prognostic significance after a myocardial infarction: the Beta-Blocker Heart Attack Trial experience.

Beta blockers represent the only documented effective long-term prophylactic treatment for patients after myocardial infarction (MI). Concern continues to be expressed about the lipid-altering effects of their long-term use, especially beta blockers without intrinsic sympathomimetic activity such as propranolol. Data collected for the Beta-Blocker Heart Attack Trial, the largest long-term clinical trial of beta-blocker use in patients after MI, have been analyzed to address the following questions. To what extent does propranolol alter lipid levels at least 6 months after MI and initiation of therapy? How predictive of subsequent coronary events and mortality are lipid levels 6 months after MI? Is there any evidence that altered lipid levels attenuate any of the beneficial effect of propranolol on coronary morbidity and mortality? By the 6-month post-MI visit, propranolol was shown to raise serum triglyceride levels by about 17% (approximately equal to 35 mg/dl) and lower serum high density lipoprotein (HDL) cholesterol by about 6% (approximately equal to 3 mg/dl). There was no effect on total cholesterol or low density lipoprotein cholesterol. In other analyses, no lipid measured 6 months after the MI was strongly predictive of subsequent coronary events or mortality. For example, every 1-mg-lower HDL value was associated with only a 0.7% relative increase in the mortality rate. Theoretically, the estimated relative increase on all-cause mortality associated with propranolol-induced HDL reduction is about 2%. In multivariate analyses adjusting for changes in HDL and serum triglyceride, propranolol-induced beneficial reductions in mortality and morbidity remained on the order of 20%, 10 times the estimated hazard.

Adult

Long term propranolol treatment and changes in body weight after myocardial infarction.

OBJECTIVE: To determine the effect of long term propranolol treatment on body weight. DESIGN: Retrospective analysis of data from a placebo controlled randomised double blind clinical trial (the beta blocker heart attack trial). PATIENTS: 3837 Men and women randomised 5-21 days after an acute myocardial infarction to treatment with placebo or propranolol for up to 40 months. Patients were followed up at annual visits. MAIN OUTCOME MEASURE: Changes in body weight. RESULTS: At the first annual visit patients treated with propranolol had gained more weight than those given placebo (mean weight gain 2.3 kg v 1.2 kg respectively, mean difference 1.2 kg (95% confidence interval 0.9 to 1.5]. These group differences remained at the second and third annual visits. The difference in weight gain could not be explained by discrepancies in the use of diuretics or in physical activity and was similar in patients of both sexes and of all ages. CONCLUSION: Long term beta blockade results in a sustained weight gain.

Double-Blind Method

Systolic hypertension in the elderly: controlled or uncontrolled.

ISH is a distinct pathogenetic entity defined by SBP readings of greater than or equal to 160 and DBP less than 90 mmHg. The etiology, although not well understood, is in some manner related to a reduction in connective tissue elasticity of large blood vessels and an increase in aortic impedance or a decrease in aortic wall compliance. The pathophysiologic consequences include an increased resistance to systolic ejection of blood and a disproportionate increase in SBP. Although not directly related, there is an important increase in peripheral vascular resistance. The prevalence of ISH in several studies is about 7 percent in those over age 60 and increases with age to nearly 20 percent in those over age 80. There is higher prevalence in females and nonwhites. The guidelines for detection of ISH are similar to those for blood pressure evaluation in general. Precautions for detection and evaluation in the elderly include multiple blood pressure measurements in the fasting state and sitting and supine blood pressure measurements before and during therapy. Pseudohypertension, although rare, should be kept in mind. There is a clear risk associated with ISH for stroke, CVD, and premature death, which increases with age and rising levels of SBP. ISH can be controlled effectively with pharmacologic therapies. A reasonable goal is a 20 mmHg reduction in systolic pressure. Proof of reduced risk for stroke, CHD, and death in those with controlled ISH remains to be demonstrated. The SHEP pilot study has demonstrated feasibility of addressing this issue. The full-scale SHEP study addresses this issue and has completed recruitment of the desired sample size and is in follow-up phase. Scheduled completion is in 1991. While we wait for the SHEP full-scale trial results, the prudent approach is for nonpharmacologic therapy and use of pharmacologic agents in that group of patients who demonstrate a large cardiovascular risk burden or increasing symptoms specifically associated with hypertension. The decision to treat must be on an individual patient basis. Pharmacologic therapy is possible in most patients with few or no adverse effects. The "low and slow" approach to therapy is helpful in minimizing these adverse effects. Low-dose diuretics have been documented to be effective in blood pressure control. Chlorthalidone, 12.5 or 25 mg per day, is suggested. Other agents, such as beta-blockers, reserpine, ACE inhibitors, and calcium channel blockers, are best used as Step 2 agents.

Aged