Educating men about prostate cancer screening. A randomized trial of a mailed pamphlet.

CONTEXT: Although evidence-based guidelines recommend that physicians inform men about prostate cancer screening, the most efficient way to do this is not known. OBJECTIVE: To evaluate whether a mailed educational pamphlet affected men's knowledge about early detection of prostate cancer. DESIGN: Randomized, controlled trial. SETTING: Primary care clinic of the Minneapolis VA Medical Center. PATIENTS: 342 men at least 50 years of age who responded to a mailed survey (overall response rate, 68%) and did not report a history of prostate cancer. INTERVENTION: "Early Prostate Cancer" pamphlet mailed to patients in the intervention group 1 week before their scheduled clinic appointments. OUTCOME MEASURES: Patients' responses to a survey mailed 1 week after their clinic appointments; prostate-specific antigen (PSA) testing determined from electronic medical records. RESULTS: Respondents were predominantly elderly white men (mean age, 71 years; 90% white) with chronic illnesses (48% described their health as "fair" or "poor"). Men who received the educational pamphlet were better informed than men in the usual care group, as measured by correct responses to the following three questions about prostate cancer screening: the natural history of prostate cancer (32% vs. 24%; P = 0.10), whether treatment lengthens lives of men with early prostate cancer (56% vs. 44%; P = 0.04), and accuracy of PSA testing (46% vs. 27%; P < 0.008). The overall proportion of correctly answered questions was greater in the intervention group (45% vs. 32%; P < 0.001). Testing for PSA in the year after the index clinic appointments did not differ significantly between the intervention group and the usual care group (31% vs. 37%; P > 0.2). CONCLUSIONS: Male veterans are poorly informed about the potential benefits and risks of prostate cancer screening. Although our mailed educational pamphlet enhanced knowledge only modestly, it was an inexpensive and easily implemented intervention.

Relation of gemfibrozil treatment and lipid levels with major coronary events: VA-HIT: a randomized controlled trial.

CONTEXT: A low plasma level of high-density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary heart disease (CHD). A secondary prevention study, the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT), demonstrated that CHD events were significantly reduced during a median follow-up of 5.1 years by treating patients with the fibric acid derivative gemfibrozil when the predominant lipid abnormality was low HDL-C. OBJECTIVE: To determine if the reduction in major CHD events with gemfibrozil in VA-HIT could be attributed to changes in major plasma lipid levels. DESIGN: Multicenter, randomized, double-blind, placebo-controlled trial conducted from September 1991 to August 1998. SETTING: The Department of Veterans Affairs Cooperative Studies Program, in which 20 VA medical centers were participating sites. PARTICIPANTS: A total of 2531 men with a history of CHD who had low HDL-C levels (mean, 32 mg/dL [0.83 mmol/L] ) and low low-density lipoprotein cholesterol (LDL-C) levels (mean, 111 mg/dL [2.88 mmol/L]). INTERVENTION: Participants were randomly assigned to receive gemfibrozil, 1200 mg/d (n = 1264), or matching placebo (n = 1267). MAIN OUTCOME MEASURE: Relation of lipid levels at baseline and averaged during the first 18 months of gemfibrozil treatment with the combined incidence of nonfatal myocardial infarction and CHD death. RESULTS: Concentrations of HDL-C were inversely related to CHD events. Multivariable Cox proportional hazards analysis showed that CHD events were reduced by 11% with gemfibrozil for every 5-mg/dL (0.13-mmol/L) increase in HDL-C (P =.02). Events were reduced even further with gemfibrozil beyond that explained by increases in HDL-C values, particularly in the second through fourth quintiles of HDL-C values during treatment. During gemfibrozil treatment, only the increase in HDL-C significantly predicted a lower risk of CHD events; by multivariable analysis, neither triglyceride nor LDL-C levels at baseline or during the trial predicted CHD events. CONCLUSIONS: Concentrations of HDL-C achieved with gemfibrozil treatment predicted a significant reduction in CHD events in patients with low HDL-C levels. However, the change in HDL-C levels only partially explained the beneficial effect of gemfibrozil.

Cardiovascular risk changes after lipid lowering medications: are they predictable?

Changes in cardiovascular risk after lipid lowering medications are generally expressed as relative risk reduction (RRR). Comparison of the eight major studies published in this last decade indicates that the RRRs ranged from a minimum (19%) for the LRC Study with cholestyramine, to maximal values of 34-37% for studies such as the HHS, 4S and AFCAPS/TexCAPS. These RRRs were barely related to the drugs' effects on major lipid parameters, e.g. LDL cholesterol. Instead, by using the absolute risk reduction (ARRs), easily calculated by subtracting the percentage end points for the drug treated from these values of the placebo group in all studies, a wide range of values was found, also adding to the series a non pharmacological study such as the Program on the Surgical Control of the Hyperlipidemias (POSCH) trial. Calculated ARRs were directly correlated to the baseline cardiovascular (CV) risk in all studies, thus allowing an easy prediction of a drug's effect in the selected population. Drugs with different mechanisms (statins, fibrates and resins) all fitted into this correlation nomogram. These findings clearly indicate that the CV effects of lipid changes, such as LDL cholesterol and triglyceride reduction or HDL rises, are in the same direction, and can be well predicted. The similar, almost identical behavior of drugs affecting LDL cholesterolemia to a different degree or not at all, indicates that novel approaches should be sought to improve risk reduction and that individual therapy should be ideally pursued, rather than a 'one drug' approach.

Triglycerides and coronary heart disease: implications of recent clinical trials.

This paper reviews the clinical trial data that offer insight into the question of whether, and in what groups of people, triglycerides might be an appropriate therapeutic target for the primary or secondary prevention of atherosclerotic cardiovascular disease. Two angiographic trials (the Lopid Coronary Angiography Trial and the Bezafibrate Coronary Atherosclerosis Intervention Trial) and three clinical endpoint trials (the Helsinki Heart Study, the Bezafibrate Infarction Prevention Study, and the VA HDL Intervention Trial) are reviewed. Hypertriglyceridemia per se is probably not an appropriate therapeutic target for the prevention of atherosclerotic cardiovascular disease because it is a poor marker of atherogenic risk and because there have been no clinical trials that have directly addressed the question of whether lowering the triglyceride level reduces the number of clinical events. The studies reviewed here, however, suggest that patients with established coronary heart disease and a high triglyceride level, in association with either a low high-density lipoprotein-cholesterol level or perhaps other features of the metabolic syndrome, such as obesity, diabetes, or hypertension, may benefit from fibrate therapy. For patients without established coronary heart disease, it is reasonable to consider hypertriglyceridemia as a risk marker prompting the aggressive treatment of other risk factors such as hypertension, diabetes, high low-density lipoprotein-cholesterol, and obesity.

Identification of clinical risk factors for nosocomial pneumococcal bacteremia.

Clinical risks for nosocomial pneumococcal bacteremia (NPB) have been analyzed previously in case series, a study design inadequate for this purpose. Therefore, we performed a case-control study of NPB, pairing each of 37 cases identified retrospectively at the Minneapolis Veterans Affairs Medical Center from the period of 1984-1994 with four or five hospitalized controls. Comorbidities identified at the time of admission that were significantly associated with NPB on univariate and multivariate analysis included respiratory or hematologic malignancy, anemia, chronic obstructive pulmonary disease, and coronary artery disease. All characteristic symptoms and signs of pneumococcal infection were significantly more common in cases than in controls. NPB was strongly associated with death within 7 days of the index blood culture date, and the mortality rate among cases was 40.5%, compared with 1.2% among nonbacteremic controls (P < .00001). We conclude that NPB is a highly lethal infection that is associated with distinct but identifiable clinical risks, symptoms, and signs.

Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group.

BACKGROUND: Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol. METHODS: We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes. RESULTS: The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels did not differ significantly between the groups. A primary event occurred in 275 of the 1267 patients assigned to placebo (21.7 percent) and in 219 of the 1264 patients assigned to gemfibrozil (17.3 percent). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We observed a 24 percent reduction in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (P< 0.001). There were no significant differences in the rates of coronary revascularization, hospitalization for unstable angina, death from any cause, and cancer. CONCLUSIONS: Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.

Simultaneous screening for three correlated lipids in the VA HDL Intervention Trial.

We developed methodology to design the multistage lipid screen for the VA HDL Intervention Trial, a randomized double-blind placebo-controlled secondary prevention clinical trial of 2531 participants. The trial aimed to determine if HDL-raising therapy reduces coronary events in men with low HDL-cholesterol and desirable LDL-cholesterol. Joint lipid distributions for HDL-cholesterol, LDL-cholesterol, and triglycerides were derived on the basis of estimates from previous studies, and simulations were performed to determine the cutpoints for excluding screenees for the three lipid parameters to be used at each recruitment stage. Operating characteristics for different screening rules are presented. Comparisons between the predicted and actual study recruitment results show good agreement in lipid characteristics and underscore the complexity of simultaneously screening on correlated continuous physiologic parameters such as lipids.

Serum carcinoembryonic antigen as an adjunct to preoperative staging of lung cancer.

OBJECTIVE: To determine whether measurement of preoperative serum carcinoembryonic antigen concentrations adds useful prognostic data to current preoperative staging of lung cancer by computed tomography, bronchoscopy, and mediastinoscopy. METHODS: A prospective cohort study of 130 consecutive patients was evaluated for suspected lung cancer from July 1991 through December 1992 at a university-affiliated Veterans Affairs Medical Center. Serum concentrations of carcinoembryonic antigen were measured before diagnosis, staging, or resection of cancer. RESULTS: Malignant disease was diagnosed by bronchoscopy, needle biopsy, mediastinoscopy, or resection in 111 of 130 patients. In the 50 patients undergoing resection with curative intent, multivariate analysis indicated that carcinoembryonic antigen was a significant predictor of survival independent of patient age, pathologic stage, histologic type, and tumor size (P=.0357). CONCLUSIONS: Elevated preoperative serum concentrations of carcinoembryonic antigen predict a poor prognosis for lung cancer independent of other conventional staging parameters and have an adjunctive role in the staging of lung cancer.

Carotid atherosclerosis in men with low levels of HDL cholesterol.

BACKGROUND AND PURPOSE: A low HDL cholesterol (HDL-C) frequently occurs in conjunction with a desirable LDL cholesterol (LDL-C) and is a risk factor for coronary heart disease (CHD). Additionally, the presence of carotid atherosclerosis is a strong and independent predictor of morbidity and mortality in patients with CHD. This article describes the prevalence and correlates of sonographically detected carotid atherosclerosis in men with low levels of HDL-C and CHD but without elevated levels of LDL-C or total cholesterol. METHODS: High-resolution B-mode ultrasonography was used to quantify intima-media wall thickness (IMT) in the common and internal carotid arteries and at the carotid artery bifurcation in 202 randomly selected male veterans with CHD and low levels of HDL-C who are participating in the VA HDL Intervention Trial. Ultrasonographic measurement of carotid artery wall stiffness was determined in a subset of 94 of these individuals. RESULTS: The mean maximum and single greatest carotid artery IMT measurements were 1.41 and 2.58 mm, respectively. The prevalence of ultrasound-detected carotid atherosclerosis as defined by a mean maximum IMT > or = 1.3 mm was 58.9% and by single maximum IMT > or = 1.5 mm was 87.1%. IMT was associated with increased age, lower extremity arterial disease, systolic blood pressure, and ultrasonographically measured carotid artery stiffness. CONCLUSIONS: Men with low levels of HDL-C and CHD but without elevated LDL-C or total cholesterol have a very high prevalence of ultrasound-detected carotid artery atherosclerosis.

Etiology and prognostic significance of eosinophilic pleural effusions. A prospective study.

STUDY OBJECTIVE: To determine the diagnostic and prognostic significance of eosinophilic pleural effusions. DESIGN: A prospective cohort study of patients undergoing thoracentesis between September 1990 and September 1995. SETTING: A university-affiliated VA Medical Center. PATIENTS: Four hundred seventy-six consecutive patients. MEASUREMENTS AND RESULTS: Eosinophilic pleural effusions were identified in 44 of the 476 patients (9.2%). Malignancy was diagnosed as frequently in eosinophilic as in noneosinophilic effusions (20.5% vs 20.1%). The only diagnoses that were significantly associated with eosinophilic effusions were idiopathic (25% vs 8%; p = 0.001) and postthoracic surgery (11% vs 3%; p = 0.023). Median survival was 7.7 months for those with a noneosinophilic effusion compared to 16.8 months for those with eosinophilia (p = 0.017). This difference in survival persisted after adjustment for age and diagnosis. CONCLUSIONS: We conclude that malignancy is as prevalent among eosinophilic as noneosinophilic pleural effusions. However, the survival of patients with pleural fluid eosinophilia may be better than that of patients with noneosinophilic effusions.

The Veterans Affairs High-Density Lipoprotein Intervention Trial: baseline characteristics of normocholesterolemic men with coronary artery disease and low levels of high-density lipoprotein cholesterol. Veterans Affairs Cooperative Studies Program High-Density Lipoprotein Intervention Trial Study Group.

This report describes the baseline characteristics of the 2,531 patients with coronary artery disease enrolled in the Veterans Affairs Cooperative Studies Program High Density Lipoprotein Intervention Trial. The population is characterized by a large percentage of elderly patients, diabetic patients, and patients with the clinical characteristics of the insulin-resistance syndrome.

Correlates and consequences of diffuse atherosclerosis in men with coronary heart disease. Veterans Affairs High-Density Lipoprotein Intervention Trial Study Group.

BACKGROUND: Peripheral atherosclerosis is a strong and independent predictor of mortality even in patients with known coronary heart disease. However, the prevalence, correlates, and potential adverse effects on quality of life associated with combined coronary heart disease and clinically evident cerebrovascular or lower-extremity atherosclerosis are not known. Identification of patients with "diffuse atherosclerosis" may enhance treatment of modifiable risk factors and alter therapeutic strategies. METHODS: We conducted a cross-sectional analysis of 2531 men younger than 73 years with coronary heart disease, low-density lipoprotein cholesterol levels of 3.62 mmol/L (140 mg/dL) or less, and high-density lipoprotein cholesterol level of 1.03 mmol/L (40 mg/dL) or less who were participating in Department of Veterans Affairs Cooperative Study 363 (the Veterans Affairs High-Density Lipo-protein Intervention Trial. Baseline demographic, medication, comorbidity, and atherosclerotic risk factor data were assessed by means of a standardized questionnaire. All plasma lipid levels were determined after a 12-hour fast by a central standardized lipid laboratory. Health status was determined by baseline reported symptoms, medical comorbidities, and the Psychological General Well-being Index. Clinically evident diffuse atherosclerosis was defined as a documented history of lower-extremity atherosclerosis or cerebrovascular disease. RESULTS: The mean age of all participants was 63.5 years. The mean plasma lipid values were as follows: total cholesterol, 4,52 mmol/L (174.6 mg/dL); high-density lipo-protein cholesterol, 0.81 mmol/L (31.5 mg/dL); low-density lipoprotein cholesterol, 2.88 mmol/L (111.2 mg/dL); and triglycerides, 1.81 mmol/L (160.6 mg/dL). Diffuse atherosclerosis was present in 525 (21%). Lower-extremity atherosclerosis was reported in 10%, while cerebrovascular disease was present in 13%. After controlling for other variables, the following factors were associated with the presence of diffuse atherosclerosis: increased age, being unmarried, being retired, having less than a high school education, increased alcohol use, hypertension, cigarette smoking, and diabetes. There was no association between lipid levels and the presence of diffuse atherosclerosis. After adjustment for age, race, and comorbidities, men with diffuse disease still had a reduced quality of life compared with men without diffuse atherosclerosis, as defined by having a greater number of clinical symptoms, lower psychological well-being scores, and more advanced or complicated coronary heart disease. CONCLUSIONS: Clinically evident diffuse atherosclerosis is common in men with coronary heart disease and low levels of high-density lipoprotein cholesterol. Because diffuse atherosclerosis is associated with a reduced quality of life and several modifiable risk factors, early detection and aggressive risk factor intervention appear justified.

Temporal trends in the prevalence of malignancy in resected solitary pulmonary lesions.

STUDY OBJECTIVE: To determine whether there has been an increase in the prevalence of malignancy among resected, indeterminate solitary pulmonary lesions (SPL) over the past 14 years. DESIGN: A retrospective review of all thoracotomies for indeterminate SPLs from 1981 through 1994. SETTING: A university-affiliated VA Medical Center. PATIENTS: Three-hundred seventy resected indeterminate SPLs (all < or = 6 cm) in 360 patients. MEASUREMENTS AND RESULTS: Virtually all patients were men with an average age of 63 +/- 9 years. The average lesion size was 2.5 +/- 1.4 cm; 71% were 3 cm or less. Overall, 79% of resected lesions were malignant; 94% of these were bronchogenic carcinomas. Granulomas accounted for more than 50% of benign lesions. The proportion of malignant diagnoses increased from 55 to 60% in 1981 to 1983 to 90 to 100% in 1990 to 1994 (p < 0.005). The increasing proportion of malignancy over time was independent of age at time of operation and lesion size. There was no significant difference in survival among patients with a malignant lesion resected in 1981 to 1983 compared with 1990 to 1994. CONCLUSION: We conclude that there has been a striking increase in the prevalence of malignancy among resected indeterminate SPLs over the past 14 years in our institution. We suspect that this trend reflects improvements in our ability to diagnose benign SPLs preoperatively, primarily through the use of CT. Our results should prompt other institutions to review their recent experience with the diagnosis of indeterminate SPLs to provide more timely information to physicians and their patients who are contemplating resection of SPLs.

Can phenytoin lower plasma fibrinogen concentrations?

A strong, independent and positive association between plasma fibrinogen concentrations and cardiovascular disease has been established. To determine if phenytoin lowers fibrinogen levels we measured plasma fibrinogen levels in a subset of participants enrolled in a randomized, placebo-controlled, double-blind clinical trial. Participants received placebo or 100 mg, 200 mg, or 300 mg/day of phenytoin for 14 weeks. Fifty-six subjects had post-treatment and 20 had pre- and post-treatment fibrinogen measurements. The phenytoin-treated subjects with post-treatment measurements had a 0.24 g/l (8%) reduction in mean fibrinogen levels compared to placebo (p = 0.3). Phenytoin may be capable of producing meaningful reductions in fibrinogen levels.

Effects of phenytoin on plasma high-density lipoprotein cholesterol levels in men with low levels of high-density lipoprotein cholesterol.

A low level of high-density lipoprotein cholesterol (HDL-C) is an important and common risk factor for coronary heart disease. Cross-sectional studies and uncontrolled clinical trials have suggested that phenytoin can significantly raise HDL-C levels. This study was undertaken to determine whether phenytoin can raise HDL-C levels in men with low levels of HDL-C. Ninety-two men currently receiving outpatient care at a Veterans Affairs medical center and with baseline HDL-C levels < or = 1.16 mmol/L (45 mg/dL) were recruited to participate in this randomized, placebo-controlled, double-blind clinical trial. Participants received a placebo or 100 mg, 200 mg, or 300 mg of phenytoin once daily for 14 weeks. Lipid levels were measured at baseline and at 6, 10, and 14 weeks. After 14 weeks of treatment, the 200-mg and 300-mg phenytoin groups together achieved a significant 10% increase in HDL-C levels compared with placebo after adjusting for differences in baseline HDL-C levels, age, and body mass index. Other lipid levels did not significantly change in the phenytoin groups compared with placebo. Average compliance was 98% or greater for each of the treatment groups. Eighteen participants dropped out of the study with similar numbers from each treatment group. Side effects were mild and mostly transient. Low doses of phenytoin are well tolerated and can effectively increase HDL-C levels in men with low levels of HDL-C.

Cholesterol in patients with coronary heart disease: how low should we go?

CLINICAL PROBLEM: To examine the evidence supporting the recent National Cholesterol Education Program (NCEP) recommendation that low to moderate levels of cholesterol should be aggressively managed in patients with coronary heart disease (CHD). METHODS: Cohort studies and clinical trials with angiographic or clinical endpoints, that included CHD patients with low to moderate levels of cholesterol, were systematically identified through a MEDLINE search and critically reviewed. SYNOPSIS: None of the cohort studies show that a moderate level of cholesterol confers significantly increased risk of CHD death, although a pooled relative risk of 1.14 (95% CI 1.08 to 1.4) suggests that there may be a slight excess risk. Of five angiographic trials of CHD patients with moderate levels of cholesterol, two demonstrated no improvement in angiographic endpoints with intensive lipid-lowering therapy and the other three are difficult to interpret since they included other interventions in addition to the cholesterol-lowering regimen. No large clinical trial with clinical endpoints has been reported for CHD patients with low to moderate levels of cholesterol. RECOMMENDATIONS: The recommendation to treat CHD patients who have low to moderate levels of cholesterol with diet or drugs is not based on convincing evidence of efficacy. This is in clear contrast to the recommendation for CHD patients with high levels of cholesterol, for whom there is definitive clinical trial evidence of benefit from cholesterol-lowering therapy. While we await clinical trial results for CHD patients with low to moderate levels of cholesterol, clinicians and patients must consider the possible disadvantages of therapy in relation to the uncertain benefit.

Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group.

In the present study we measured fasting lipid profiles in over 8,500 community-living men with coronary artery disease (CAD) to determine the distribution of lipid abnormalities in this population: 81% were white and 16% black; mean age 62.9 +/- 8 years; mean total cholesterol 214 +/- 41 mg/dl; low-density lipoprotein (LDL) cholesterol 140 +/- 37 mg/dl; high-density lipoprotein (HDL) cholesterol 39 +/- 11 mg/dl; and triglycerides 190 +/- 142 mg/dl. After adjusting for age, the only significant difference between blacks and whites was a higher HDL cholesterol in blacks (45 vs 38 mg/dl, p < 0.003). With use of cut points established by the National Cholesterol Education Program, 87% of subjects had high LDL cholesterol (> or = 100 mg/dl), 38% had low HDL cholesterol (< 35 mg/dl), and 33% had high triglycerides (> 200 mg/dl). We estimated that 42% of men with CAD would be definite candidates for cholesterol-lowering medication according to the National Cholesterol Education Program guidelines and that 41% of those in whom cholesterol-lowering medication would not be definitely indicated had low levels of HDL cholesterol. We conclude that (1) black men with CAD have substantially higher HDL cholesterol than white men, (2) almost 90% of male patients with CAD are candidates for dietary intervention and > 40% may need medications to lower LDL cholesterol, and (3) 40% of patients without a definite indication for cholesterol-lowering medications have low levels of HDL cholesterol.