Hypertension Is Associated with White Matter Disruption in Apparently Healthy Middle-Aged Individuals.

BACKGROUND AND PURPOSE: Traditional cardiovascular risk factors have been associated with white matter disease. Because hypertension results in vascular stiffness and impaired cerebral perfusion, we hypothesized that it would be the most relevant risk factor for microstructural white matter disruption in apparently healthy middle-aged individuals with a family history of early-onset coronary artery disease. MATERIALS AND METHODS: This was a cross-sectional analysis of participants in the Genetic Study of Atherosclerosis Risk with DTI. Regional fractional anisotropy of 181 segmented brain regions was measured using Eve WM Atlas. Risk factors were examined using univariate analysis for 48 regions representing deep WM structures. Minimal multivariable linear regression models adjusting for age, sex, and race and maximal linear regression models adjusting for cardiovascular risk factors were performed for regions meeting the Bonferroni threshold in the initial analysis. RESULTS: Included were 116 subjects (mean age, 49 ± 11 years; 57% men) with a moderate load of cardiovascular risk factors. Subjects with hypertension had significantly lower regional fractional anisotropy in the right cingulum and left stria terminalis in the minimal and maximal regression models. Additionally, there was lower regional fractional anisotropy in the left fornix in the maximal model and right sagittal stratum in the minimal model. Systolic blood pressure values were significantly associated with regional fractional anisotropy in the left superior longitudinal fasciculus in the maximal model. There were no significant differences among regional fractional anisotropy values for other cardiovascular risk factors. CONCLUSIONS: In middle-aged apparently healthy individuals with susceptibility to vascular disease, among all known cardiovascular risk factors, hypertension was associated with microstructural WM disruption.

Heritability of platelet function in families with premature coronary artery disease.

BACKGROUND: Variations in platelet function among individuals may be related to differences in platelet-related genes. The major goal of our study was to estimate the contribution of inheritance to the variability in platelet function in unaffected individuals from white and African American families with premature coronary artery disease. METHODS: Platelet reactivity, in the absence of antiplatelet agents, was assessed by in vitro aggregation and the platelet function analyzer closure time. Heritability was estimated using a variance components model. RESULTS: Both white (n = 687) and African American (n = 321) subjects exhibited moderate to strong heritability (h(2)) for epinephrine- and adenosine diphosphate-induced aggregation (0.36-0.42 for white and >0.71 for African American subjects), but heritability for collagen-induced platelet aggregation in platelet-rich plasma was prominent only in African American subjects. Platelet lag phase after collagen stimulation was heritable in both groups (0.47-0.50). A limited genotype analysis demonstrated that the C825T polymorphism of GNB3 was associated with the platelet aggregation response to 2 muM epinephrine, but the effect differed by race. CONCLUSIONS: Considering the few and modest genetic effects reported to affect platelet function, our findings suggest the likely existence of undiscovered important genes that modify platelet reactivity, some of which affect multiple aspects of platelet biology.

Fusion of adenovirus E1A to the glucocorticoid receptor by high-resolution deletion cloning creates a hormonally inducible viral transactivator.

The 289-amino-acid E1A protein of adenovirus type 2 stimulates transcription from early viral and certain cellular promoters. Its mechanism is not known, and there exist no temperature-sensitive mutants of E1A that could help to elucidate the details of E1A transcriptional activation. To create for E1A such a conditional phenotype, we fused portions of E1A to the human glucocorticoid receptor (GR) to make transactivation by E1A dependent on the presence of dexamethasone. Nested subsets of the E1A coding region, centered around the 46-amino-acid transactivating domain, were substituted for the DNA-binding domain of the GR. One of the resulting chimeric proteins (GR/E1A-99), which included the entire E1A transactivating domain, stimulated expression from a viral early promoter (E3) exclusively in the presence of hormone. GR/E1A-99 did not transactivate a GR-responsive promoter. It therefore exhibited the promoter specificity of E1A while possessing the hormone inducibility of the GR. Two smaller chimeras that contained only portions of the E1A transactivating domain failed to transactivate E3. These three chimeras were constructed by a novel strategy, high-resolution deletion cloning. In this procedure, series of unidirectional deletions were made with exonuclease III on each side of the E1A coding region at a resolution of 1 to 2 nucleotides. The large number of in-frame fragments present in the collection of deleted clones facilitated the construction of the GR/E1A chimeras and can be used to create many additional fusions.

Risk factors in siblings of people with premature coronary heart disease.

Prior studies of the contribution of coronary disease risk factors to familial aggregation of premature coronary disease may have underestimated risk factors by relying on self-reported risk factor prevalence levels or, when risk factors have been measured, by using cut points in excess of the 90th percentile. To determine the actual prevalence of hyperlipidemia, hypertension and diabetes, and the awareness of these coronary risk factors in unaffected family members, 150 apparently coronary disease-free siblings of 86 people who had documented coronary disease before 60 years of age were studied. All subjects participated in a 1 day screening preceded by a self-administered risk factor questionnaire and a personal interview. Participation of both the index patients and siblings exceeded 86%. With the use of nationally established recommendations for blood pressure and lipids, which are based on coronary disease risk curves, screening revealed that 48% of brothers and 41% of sisters were hypertensive, 45% of brothers and 22% of sisters had a lipid abnormality, 38% of siblings were current cigarette smokers and 4.7% were diabetic. Two or more risk factors were present in 42% of brothers and 26% of sisters. More than 75% of siblings had one or more risk factors that would require intervention. When compared with a race-, gender- and age-matched reference population from the Lipid Research Clinics Prevalence Study, distributions for blood pressure and for total and low density lipoprotein cholesterol were higher for the siblings in every gender and age group.(ABSTRACT TRUNCATED AT 250 WORDS)

Cancer screening and informed patient discussions. Truth and consequences.

While screening for asymptomatic cancer has become one of the principal clinical activities of primary care physicians, patients are generally not involved directly in screening decisions. To help physicians better communicate the potential benefits and burdens of cancer screening, this article concisely presents information necessary for patients to make a reasoned decision as to whether to proceed with screening: the probability of developing cancer, the operating characteristics of available screening tests, the likelihood that screening will result in an improved outcome for the individual patient, and the potential burdens associated with screening. Screening tests for breast, colorectal, cervical, and prostate cancers are reviewed, including mammography, clinical breast examination, fecal occult blood testing, Papanicolaou smear, digital rectal examination, and prostate-specific antigen. Better communication about cancer screening will promote shared decision making--a central tenet of the physician-patient relationship.

Calf deep venous thrombosis. A wolf in sheep's clothing?

To determine the natural history of calf deep venous thrombosis (C-DVT), an analytic review of the 20 relevant English-language papers published since 1942 was performed. Remarkably little methodologically sound research on this subject was found. However, available evidence suggests that C-DVT propagates to the thigh in up to 20% of cases and that propagation invariably occurs before embolization. No fatal emboli were reported in patients presenting with isolated C-DVT. Traditional anticoagulation treatment with heparin sodium and warfarin sodium of symptomatic patients with C-DVT appears to prevent extension, embolization, and early recurrence. There is no convincing evidence that C-DVT leads to chronic venous insufficiency or whether the risks of anticoagulation exceed the risks of no treatment. As an option to anticoagulation, physicians may choose to follow patients with C-DVT with serial impedance plethysmography, treating only if there is evidence of proximal extension.

Axillary and subclavian venous thrombosis. Prognosis and treatment.

To clarify the prognosis of axillary and subclavian deep venous thrombosis and to determine which clinical factors influence its sequelae, we systematically reviewed the English-language literature published on this subject since 1950. Seventy-one case reports and 17 case series describing a total of 329 patients met our inclusion criteria for detailed review. There were major deficiencies in the quality, as well as quantity, of the available clinical data: few patients were enrolled at axillary and subclavian deep venous thrombosis inception, and outcome assessments were susceptible to bias and based on insensitive diagnostic tests. Posttreatment symptoms were reported in 34% of cases, pulmonary embolism in 9.4% (one half documented by lung scan or angiography), and death in 1.2% (three of four deaths due to pulmonary emboli). These complications occurred regardless of etiologic category (spontaneous, catheter related, or miscellaneous). Thrombolytic agents and surgery, in addition to anticoagulation, were often used to treat axillary and subclavian deep venous thrombosis, but there were no controlled trials to support any one approach. Until such trials are performed, therapy should be based on the anticoagulation regimens proved to be effective for deep venous thrombosis of the lower extremity. In selected patients, thrombolytic therapy and surgery may have important roles.

The costs of employee smoking. A computer simulation of hospital nurses.

A computer simulation model of the economic impact of employee smoking on an employer was developed with a population of hospital nurses as the example. Net economic impact was calculated by estimating cumulative costs borne by the employer under various scenarios and comparing them with projected costs estimated from baseline data. The model included the following: baseline number of staff, baseline percentage of smokers, annual employee turnover rate, number of smokers interested in quitting, the cost of a smoking cessation program, expected success rate of a voluntary cessation program, smokers quitting spontaneously without a program, and employer-borne costs related to employee smoking. A variety of scenarios were constructed to generate a range of employer net economic impact figures and resulting percentages of smoking employees. Results showed that the benefits of a cessation program would be eliminated over several years, unless the prevalence of smoking in incoming employees was reduced. The most favorable scenario, combining a hospital cessation program and reduced smoking among new employees, generated cumulative savings, discounted at 5%, of $358,000 to $684,000 over an eight-year period.

Optimal management of suspected lower-extremity deep vein thrombosis. An evaluation with cost assessment of 24 management strategies.

Traditionally, patients suspected to have lower-extremity deep vein thrombosis have undergone venography, which is invasive, is expensive, and may cause deep vein thrombosis in healthy individuals. Recent studies have shown the safety and efficacy of alternative noninvasive approaches that employ impedance plethysmography or real-time ultrasonography. We compared these tests using decision analysis to model the consequences of 24 different management strategies for ambulatory patients suspected to have deep vein thrombosis. We also calculated the incremental cost per additional life saved for each strategy. Our analysis revealed that the optimal approach was to perform real-time ultrasonography followed by anticoagulation therapy if deep vein thrombosis is found. This approach was both effective and cost saving compared with no testing or treatment. Serial follow-up studies of patients whose initial study suggested no DVT saved additional lives, but at a cost of $390,000 per each additional life saved for patients with one follow-up study and $3.5 million per each additional life saved for patients with a second follow-up study. Venography should play a limited role in the contemporary evaluation of patients suspected to have deep vein thrombosis. Future research should focus on the determination of clinical predictors of patients who should undergo serial examinations.

Inferior vena cava filters. Indications, safety, effectiveness.

BACKGROUND: Preventing pulmonary embolization by interrupting vena caval flow has been attempted since 1893. Inferior vena cava (IVC) filters have been available for 20 years, and currently there are five filters commercially available in the United States (Greenfield filter, Titanium Greenfield filter, Simon-Nitinol filter, Bird's Nest filter, and LGM or Vena Tech filter) and two other filters under development (Amplatz filter and Günther filter). Although these devices are widely used, their clinical utility and safety have not been completely evaluated. Controlled clinical trials to determine the clinical role for IVC filters have not been attempted, but numerous case series describing the outcomes of the seven current filters have been published. We have systematically reviewed these studies to clarify what is known about the indications, safety, and effectiveness of IVC filters. METHODS: Using the MEDLINE database, all English-language publications since 1970 that included follow-up clinical information after filter insertion were reviewed and eight methodologic guidelines were employed to assess the scientific quality of the clinical information. RESULTS: Twenty-four case series were reviewed: 16 concerned the Greenfield filter (1632 patients), and eight dealt with newer designs (925 patients). Commonly noted methodologic problems included failure to report the initial extent of thromboembolic disease, incomplete description of the patient assembly process, and incomplete and potentially biased outcome assessment. Recurrent clinical pulmonary embolism was rare after filter placement, and only eight deaths from pulmonary embolism were reported. Filter complications were common but rarely life threatening; four (0.16%) deaths from filter complications were noted among the reviewed studies. Thrombotic complications following filter placement included insertion-site deep vein thrombosis and IVC obstruction. These events were rare, but they occurred with all filter types. CONCLUSIONS: Inferior vena cava filters appear to be effective in preventing recurrent pulmonary embolism. Despite the large published experience with IVC filters, many questions remain about their indications, safety, and effectiveness. Anticoagulant therapy, if not contraindicated, should be used in conjunction with filters. While there is no ideal filter, some situations call for specific filters. Filter selection and insertion require experience, modern angiographic technique, and collaboration between clinicians caring for patients and the interventional radiologists or surgeons inserting the device.

Accuracy of laboratory and portable monitor international normalized ratio determinations. Comparison with a criterion standard.

BACKGROUND: Portable instruments that measure the prothrombin time and automatically calculate the international normalized ratio (INR) with the use of a drop of whole blood have simplified the treatment of patients who are receiving warfarin therapy. The accuracy of these portable monitors has never been determined by comparing INR results with a criterion (gold) standard INR determination. METHODS: Duplicate whole-blood INR determinations were made with two commercially available portable INR monitors. Duplicate frozen-plasma samples were measured with four different thromboplastin reagents, each with a different international sensitivity index. The criterion standard INR was determined by using an international reference thromboplastin and the manual tilt-tube technique. Agreement was evaluated by determining how accurately laboratory and monitor INR determinations matched criterion standard values in designating a sample to be within or outside of currently recommended INR target ranges. RESULTS: Two of the laboratory methods, which used relatively sensitive thromboplastins, showed close agreement with the criterion standard, whereas two laboratory methods that used less sensitive thromboplastin reagents showed poor agreement. Both of the portable monitors fell between these extremes. The two best laboratory methods ere significantly better (P < .003) than both monitors, which in turn were better (P < .003) than the remaining two laboratories. CONCLUSIONS: There is large interlaboratory variation in the accuracy of INR determinations. Laboratory methods that used insensitive (high international sensitivity index) thromboplastins performed poorly. Accuracy of monitor measurements appears satisfactory.

D-dimer testing and acute venous thromboembolism. A shortcut to accurate diagnosis?

D-dimer fragments can be measured easily in plasma and whole blood, and the presence or absence of D-dimer could be useful in the diagnostic evaluation of venous thromboembolism. We systematically reviewed the English literature for articles that compared D-dimer results with those of other tests for deep venous thrombosis or pulmonary embolism. Twenty-nine studies were selected for detailed review, and we noted wide variability in assay performance, heterogeneity among subjects, and failure to define absence or presence of venous thromboembolism by a comprehensive criterion standard for diagnosis. These methodologic problems limit the generalizability of the published estimates of D-dimer accuracy for deep venous thrombosis or pulmonary embolism, and the clinical utility of this potentially important test remains unproved.

The role of spiral volumetric computed tomography in the diagnosis of pulmonary embolism.

To evaluate the evidence for the use of spiral volumetric computed tomography (SVCT) in the diagnosis of acute pulmonary embolism (PE), the 11 English-language studies published through July 1998 that compared SVCT with a reference standard for PE were systematically reviewed. Among the reviewed studies, methodological problems were common. Only 5 of these studies fulfilled 5 of 11 basic standards addressing important issues in diagnostic test research. The reported sensitivities of SVCT compared with pulmonary angiography varied widely (64%-93%), which was likely the result of differences in study populations. Spiral volumetric computed tomography may be relatively sensitive and specific for diagnosing central pulmonary artery PEs, but it is insensitive for diagnosing subsegmental clots. Spiral volumetric computed tomography may have a role as a "rule-in" test for large central emboli, but additional research is required to establish its place in clinical practice.

Nurse-mediated cholesterol management compared with enhanced primary care in siblings of individuals with premature coronary disease.

BACKGROUND: Siblings of individuals with premature coronary heart disease have a high prevalence of low-density lipoprotein cholesterol (LDL-C) levels requiring treatment. OBJECTIVE: To evaluate management strategies for high LDL-C levels in apparently healthy 30- to 59-year-old siblings of individuals with documented coronary heart disease prior to age 60 years. METHODS: In a 2-year trial of care provided by either a nurse trained in lipid management (NURS) or enhanced primary care (EPC), in which physicians received recommendations based on national guidelines, 156 siblings with LDL-C levels of 4.14 mmol/L (160 mg/dL) were randomized by family. The LDL-C goal levels below 3.36 mmol/L (130 mg/dL) were compared between and within intervention groups. Multiple logistic regression analyses were applied to predict 2-year achievement of the goal. RESULTS: The NURS group achieved a significantly greater percentage of goal LDL-C levels than the EPC group (26% vs 10%; P=.008). The NURS LDL-C levels decreased an average of 0.91 mmol/L (35 mg/dL) while EPC levels decreased by 0.52 mmol/L (24 mg/dL) (P=.09). In the final multivariate model, siblings taking lipid-lowering drug treatment were 6.02 times more likely (95% confidence interval, 2.24-16.18) than those not receiving pharmacotherapy to achieve LDL-C goals; nurse management (P=.09) was marginally significant. Pharmacotherapy was instituted in 45.2% of NURS and 16.7% of EPC siblings (P=.001). CONCLUSIONS: High LDL-C levels in siblings were more effectively treated by a trained nurse, probably related to greater adherence to the application of national guidelines. Nonetheless, the majority of siblings with high LDL-C levels did not meet goal levels 2 years after an index case coronary heart disease event.

Prevalence of hypercholesterolemia among siblings of persons with premature coronary heart disease. Application of the Second Adult Treatment Panel guidelines.

BACKGROUND: Increased blood cholesterol, specifically high low-density lipoprotein cholesterol, increases risk for coronary heart disease (CHD). Persons with a positive family history of premature CHD also are at markedly increased risk. OBJECTIVE: To examine the prevalence of hypercholesterolemia based on the second report of the National Cholesterol Educational Program Adult Treatment Panel (ATP II) guidelines in the asymptomatic healthy siblings of people with premature CHD. METHODS: A total of 668 asymptomatic healthy siblings (354 men and 314 women) underwent screening for risk factors for CHD. Siblings were categorized into treatment categories for primary prevention defined by ATP II. The percentage who were candidates for intervention were compared with the published national estimates for those without CHD from the third National Health and Nutrition Examination Survey (NHANES III). RESULTS: Based on ATP II guidelines, 65% of the asymptomatic adult siblings required fasting lipoprotein analysis compared with 33% of adults without CHD in the national reference population. Of the siblings who met the criteria for fasting lipoprotein analysis, most (56%) were candidates for dietary therapy, more than twice the proportion of adults from NHANES III. The percentage of the siblings who qualified for drug intervention and dietary therapy was 3 times greater than the national sample, 33% vs 11%, respectively. Assuming a 10% hypothetical reduction in low-density lipoprotein cholesterol levels as the result of dietary modification, the proportion of the sibling sample who were possible candidates for drug therapy was 20%, still 4 times that predicted for the national sample. CONCLUSIONS: These results underscore the need for aggressive detection and treatment of hypercholesterolemia in this easily identifiable high-risk population of siblings of people with premature CHD.

Hypertension among siblings of persons with premature coronary heart disease.

To determine the extent to which the Fifth Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure (JNC-V) guidelines were implemented in high-risk families with premature coronary heart disease, we examined the prevalence of hypertension and associated coronary risk factors in asymptomatic siblings of persons with documented premature coronary disease (<60 years of age). A total of 859 apparently healthy siblings (51% male, 19% African American) were screened for coronary risk factors. Siblings were classified as normotensive or hypertensive (BP > or = 140/90 and/or current antihypertensive pharmacotherapy). The prevalence of hypertension, awareness, treatment, and control among siblings was compared with published national estimates from the third National Health and Nutrition Examination Survey. The prevalence of hypertension in siblings was 44%. Among all hypertensives, only 60% were aware of being hypertensive, 45% were being treated, and 16% were under control. A high prevalence of other coronary risk factors was found among hypertensive siblings: 72% were hypercholesterolemic; 61% were obese; 29% were current smokers; 82% were consuming >30% of calories from fat; and only 14% were participating in vigorous physical activity three or more times per week. Comparisons with the national reference population revealed siblings to have a significantly higher prevalence of hypertension, along with significantly lower levels of awareness, treatment, and control. These findings demonstrate the intersection of multiple risk factors among hypertensive siblings and emphasize the need for more aggressive screening and treatment in this easily identifiable high-risk population.

The neurological manifestations of porphyria: a review.

The hereditary hepatic porphyrias, PV, AIP and HC, are characterized biochemically by increased excretion of porphyrins and the porphyrin precursors ALA and PBG. They are characterized clinically by episodes of acute neurological involvement. The increased production of porphyrins and porphyrin precursors has been shown to be due to partial enzyme blocks along the heme biosynthetic pathway which results in secondary depression of the key enzyme ALA-synthetase. The neurological manifestations could therefore be related to either a decrease in essential heme-proteins or other heme-containing compounds within the nervous system, or to a toxic effect of the over-production of the porphyrin precursors ALA and PBG. There is evidence for and against both theories. Recent work from a number of research groups has shown the porphyrin precursors to have potent pharmacological effects on the nervous system, and these are possibly related to the GABA receptor and binding site-porphyrin precursor interactions. Current studies on therapy of the acute attack have concentrated on suppression of ALA-synthetase activity, and consequently, on reduced ALA and PBG production. A number of such methods of therapy have met with remarkable success and hold promise for the future treatment of the acute attack.

Lipoamide dehydrogenase: rapid heat inactivation in platelets of patients with recessively inherited ataxia.

The activity of lipoamide dehydrogenase was abnormally heat-labile in homogenized platelets from seven patients with as recessive ataxia conforming to the syndrome of Friedreich ataxia or clinical variants. Taken together, the abnormality and previous findings of low activity and abnormal kinetic properties are compatible with a change in the conformation of the enzyme in these patients.

The effect of fasting status on the determination of low-density and high-density lipoprotein cholesterol.

PURPOSE: To determine the effect of a self-selected meal on concentrations of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in a screening setting and to determine the effect of using nonfasting values to classify individuals according to National Cholesterol Education Program guidelines. SUBJECTS AND METHODS: Study subjects were 115 employees who had previously participated in worksite total cholesterol screening, selected by stratified random sampling for sex and total cholesterol levels. Total cholesterol, triglycerides, HDL-C, and estimated LDL-C were determined before subjects ate a self-selected breakfast and 3 and 5 hours after eating it. RESULTS: LDL-C values determined 3 and 5 hours following breakfast were approximately 7% and 2.5% lower, respectively, than fasting values. Use of 3-hour and 5-hour LDL-C determinations to classify individuals with elevated fasting levels (> or = 3.36 mmol/L) resulted in false-negative rates of 20% and 14%, respectively. Three- and 5-hour HDL-C values were approximately 4% and 1.5% lower, respectively, than fasting levels. Use of 3-hour HDL-C values to classify individuals with low fasting levels (< 0.91 mmol/L) resulted in no false-negatives, whereas 1 of 7 individuals with low fasting HDL-C was misclassified when 5-hour values were used. CONCLUSIONS: These results support the 1993 National Cholesterol Education Program guidelines that LDL-C levels should be determined only in fasting persons, and that nonfasting HDL-C values may be acceptable for screening purposes.

Relationship between corticosteroid exposure and plasma lipid levels in heart transplant recipients.

PURPOSE: Accelerated coronary atherosclerosis is a major cause of heart graft failure two years and more after heart transplantation, yet its etiology remains undetermined. We conducted this study to determine the prevalence of coronary risk-associated lipid abnormalities, and the relationship between lipid levels and exposure to corticosteroids and cyclosporine, in heart transplant recipients. PATIENTS AND METHODS: The records of 92 consecutive heart transplant recipients from three different transplantation centers were reviewed. Patients from the three centers varied in age, in corticosteroid regimens, and in the proportion undergoing transplantation for ischemic cardiomyopathy. Although 11 patients were not receiving corticosteroids at the time of the study, all patients had received them immediately after transplantation. In addition to information pertaining to demographics, pretransplant medical history, rejection episodes, drug doses, renal function, and blood glucose levels, data on dietary intake and body weight were collected and plasma lipid levels were measured at the time of record review. RESULTS: A significant number, 48 (52 percent), of heart transplant recipients were above the sex- and age-adjusted 75th percentile, and 35 (38 percent) were above the 90th percentile for total cholesterol in comparison with a general reference population. Similar elevations were found in low-density lipoprotein cholesterol, triglyceride, and high-density lipoprotein cholesterol levels. Bivariate analysis demonstrated cumulative prednisone exposure (r = 0.40, p = 0.0001) and cumulative cyclosporine exposure (r = 0.22, p = 0.04) but not diet or etiology of pretransplant heart disease to be significantly associated with age- or sex-adjusted total cholesterol percentiles. Low-density lipoprotein cholesterol percentiles were also correlated with cumulative prednisone (r = 0.37, p = 0.001) and cumulative cyclosporine exposure (r = 0.24, p = 0.02). Stepwise multiple linear regression analysis, however, demonstrated cumulative prednisone exposure to be the strongest predictor of both total and low-density lipoprotein cholesterol levels and percentiles (p = 0.0001), independent of cumulative cyclosporine exposure and other clinical variables. CONCLUSION: These data suggest that long-term corticosteroid exposure may result in an increased prevalence of unfavorable lipid profiles in heart transplant recipients.