D L Sprecher

Cleveland Clinic, Cleveland, OH, United States

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Publications (60)374.55 Total impact

  • The American Journal of Cardiology 04/2003; 91(5):575-80. · 3.21 Impact Factor
  • J.P. Frolkis, G.L. Pearce, D.L. Sprecher
    The American Journal of Cardiology 01/2002; 89(6). · 3.21 Impact Factor
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    ABSTRACT: Myeloperoxidase (MPO), a leukocyte enzyme that promotes oxidation of lipoproteins in atheroma, has been proposed as a possible mediator of atherosclerosis. To determine the association between MPO levels and prevalence of coronary artery disease (CAD). Case-control study conducted from July to September 2000 in a US tertiary care referral center, including 158 patients with established CAD (cases) and 175 patients without angiographically significant CAD (controls). Association of MPO levels per milligram of neutrophil protein (leukocyte-MPO) and MPO levels per milliliter of blood (blood-MPO) with CAD risk. Leukocyte- and blood-MPO levels were both significantly greater in patients with CAD than in controls (P<.001). In multivariable models adjusting for traditional cardiovascular risk factors, Framingham risk score, and white blood cell counts, MPO levels were significantly associated with presence of CAD, with an OR of 11.9 (95% CI, 5.5-25.5) for the highest vs lowest quartiles of leukocyte-MPO and an OR of 20.4 (95% CI, 8.9-47.2) for the highest vs lowest quartiles of blood-MPO. Elevated levels of leukocyte- and blood-MPO are associated with the presence of CAD. These findings support a potential role for MPO as an inflammatory marker in CAD and may have implications for atherosclerosis diagnosis and risk assessment.
    JAMA The Journal of the American Medical Association 11/2001; 286(17):2136-42. · 29.98 Impact Factor
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    ABSTRACT: Recent studies have supported the hypothesis that calcific aortic stenosis is the product of an active inflammatory process, with similarities to atherosclerosis. We sought to determine whether therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) might slow the progression of aortic stenosis. A retrospective study of 174 patients (mean age 68+/-12 years) with mild to moderate calcific aortic stenosis was conducted. Patients required normal left ventricular function, </=2+ aortic regurgitation, and >/=2 echocardiograms performed at least 12 months apart. Fifty-seven patients (33%) received treatment with a statin; the remaining 117 (67%) did not. The statin group was older and had a higher prevalence of hypertension, diabetes mellitus, and coronary disease. During a mean follow-up of 21 months, patients treated with statin had a smaller increase in peak and mean gradient and a smaller decrease in aortic valve area. When annualized, the decrease in aortic valve area for the nonstatin group was 0.11+/-0.18 cm(2) compared with 0.06+/-0.16 cm(2) for those treated with a statin (P=0.03). In multivariate analysis, statin usage was a significant independent predictor of a smaller decrease in valve area (P=0.01) and a lesser increase in peak gradient (P=0.02). Statin-treated patients, despite a higher risk profile for progression, had reduced aortic stenosis progression compared with those not treated with a statin. These data provide justification for a prospective randomized trial to substantiate whether statin therapy slows the progression of aortic stenosis.
    Circulation 10/2001; 104(18):2205-9. · 15.20 Impact Factor
  • D L Sprecher
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    ABSTRACT: A number of reports demonstrate the importance of serum triglyceride values in predicting the clinical onset of vascular disease. However, adjustment for measurements highly correlated with triglyceride (TG) levels, such as history of diabetes, body mass index, and high-density lipoprotein cholesterol (HDL-C), lessen if not remove the TG contribution to outcomes. More recently, improved analytic approaches have more persuasively implicated triglycerides as independently relevant to the onset of cardiovascular disease. Elevated TG values are the consequence of larger TG-rich particles, including very low density lipoprotein and atherogenic intermediate particles, which are in turn associated with dense low-density lipoprotein. It has been observed that a reduction in TG concentrations often proceeds in parallel with improved clinical outcomes; however, direct correlation between the two has been elusive. This has been demonstrated in multiple pharmacologic trials. However, an improvement in these relationships has been observed when TG-correlated measurements of intermediate particles, low-density lipoprotein density, and HDL-C have been made. National guidelines for cholesterol treatment have now incorporated a TG greater than 200 mg/dL as a secondary treatment trigger, which targets apolipoprotein B-related particles, represented by non-HDL-C (total cholesterol minus HDL-C), as the suggested goal of therapy.
    Current Cardiology Reports 10/2001; 3(5):424-32.
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    D L Sprecher, J P Frolkis
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    ABSTRACT: The third Adult Treatment Panel guidelines from the National Cholesterol Education Program, released in May 2001, depart from previous guidelines in several ways. As in previous guidelines, treatment and treatment goals are based not only on lipid levels but also on the patient's risk status. The method for calculating risk, however, has been refined considerably. Patients are classified in the highest-risk group if they have any of these disorders: known coronary artery disease, diabetes mellitus, peripheral vascular disease, abdominal aortic aneurysm, carotid artery disease, or a 10-year risk of a coronary event of more than 20% (as determined by use of a scoring method).
    Cleveland Clinic Journal of Medicine 08/2001; 68(7):617-22. · 3.40 Impact Factor
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    ABSTRACT: Hyperlipidemia is a risk factor for the progression of coronary artery disease, and possibly also valvular aortic stenosis. Thus, patients with aortic stenosis, coronary disease (or both) might be expected to have more abnormal lipid profiles than those without these two conditions. The lipid profiles of patient subsets undergoing aortic valve replacement (AVR) with or without concomitant coronary artery bypass grafting (CABG), as well as those undergoing isolated CABG, between 1987 and 1997 were analyzed retrospectively. Four surgical groups were identified: AVR for aortic regurgitation (n = 370); AVR for predominant aortic stenosis (n = 1,072); AVR for aortic stenosis (AS) with CABG (n = 914); and isolated CABG (n = 11,156). The complete fasting lipid profiles of patients were collected, analyzed by group, and compared. Analysis by Spearman's correlation showed that total cholesterol levels, triglycerides and low-density lipoproteins (LDL-C) were modestly, yet significantly, increased in each successive group, while high-density lipoproteins were decreased. AS patients undergoing isolated AVR had significantly higher total cholesterol (215 versus 201 mg/dl; p <0.0001), triglycerides (125 versus 104 mg/dl; p <0.0001) and LDL-C (139 versus 132 mg/dl; p = 0.003) than those undergoing AVR for aortic regurgitation. Total cholesterol >200 mg/dl was significantly associated with AS, even after adjusting for differences in age, sex, diabetes mellitus and hypertension, with an odds ratio of 1.5 (95% confidence interval, 1.2-2.0; p = 0.001). Progressively abnormal lipid profiles are associated with AS and coronary disease in patients undergoing AVR. This evidence helps to extend the link between dyslipidemia and AS in a large consecutive series of patients.
    The Journal of heart valve disease 01/2001; 10(1):19-24. · 1.07 Impact Factor
  • D L Sprecher
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    ABSTRACT: A growing number of trials that used fibrates and niacin alone or in combination with other lipid-altering agents have shown that both these drugs are effective for reducing total cholesterol, low-density lipoprotein cholesterol (LDL-C) and triglycerides, and for increasing high-density lipoprotein cholesterol (HDL-C) levels. These lipid changes are associated with a reduction in events such as fatal and nonfatal myocardial infarction, stroke, and transient ischemic attack. In angiographic trials, they are associated with disease regression, increased minimal luminal diameter, and protection from risk of new lesions. In a head-to-head comparison study, niacin 2,000 mg/day increased HDL-C more than gemfibrozil 1,200 mg/day, and decreased the total cholesterol-to-HDL-C ratio, lipoprotein (a) (Lp[a]), and fibrinogen levels significantly more. Combination therapies of niacin plus a resin or statin are effective, well tolerated, and safe.
    The American Journal of Cardiology 01/2001; 86(12A):46L-50L. · 3.21 Impact Factor
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    J M Foody, J A Milberg, G L Pearce, D L Sprecher
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    ABSTRACT: Lipoprotein (a) has been associated with increased coronary artery disease (CAD) risk in men, but relatively little data exists in women. While age influences the cardiovascular risk associated with Lp(a) in men, little is known about this phenomenon in women. The impact of gender on Lp(a) has not been fully studied in an ongoing clinical practice. Baseline Lp(a) values were measured in 918 CAD and 829 non-CAD patients (603 females, 1144 males) entering an outpatient prevention clinic. The age-specific association of elevated Lp(a) (> 30 mg/dl) with CAD was examined after adjustment for traditional risk factors. Lp(a) was a significant risk factor (OR = 1.9, CI, 1.4-2.6) in men and women (OR = 1.9, CI 1.3-2.9). In men age < or = 55 years the odds ratio for increased cardiovascular risk in high vs low Lp(a) was 2.5 (CI 1.6-3.9). In men < or = 55, CAD increased from 32 to 61% as Lp(a) progressively rose from < or = 5 to > or = 45 mg/dl (P value for trend < 0.001). No significant increase was observed in men > 55 years (OR = 1.3, CI 0.9-2.1). In women < or = 55 years, the risk of CAD increased from 22 to 35% (OR 1.6, CI 0.8-3.2), and increased from 38 to 63% in women > 55 (OR 2.1, CI 1.3-3.5). Further, of high-risk patients (men < or = 55 and women > 55 years) with an Lp(a) in the range of 20-44 mg/dl (third quartile), younger men showed a greater incidence of CAD (51%) than older women (43%). Both genders revealed substantial risk when the Lp(a) values were above 45 mg/dl. (OR = 3.7, CI = 2.0-6.8 in younger men; OR = 3.3, CI = 1.6-6.6 in older women). In this cross sectional study of both men and women, elevated Lp(a) was associated with a significantly increased risk of CAD in men and women. While we corroborate previous reports on the lack of association in older men, the determination of an enhanced Lp(a)-related risk in older women was new and unanticipated. Further, in this population of high risk patients, substantial cardiovascular risk appeared to be represented by higher concentrations of Lp(a) in women than observed in men.
    Atherosclerosis 12/2000; 153(2):445-51. · 3.71 Impact Factor
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    ABSTRACT: Hypertriglyceridemia is commonly observed in association with diabetes. Despite cross-sectional studies and isolated longitudinal analyses in patients without coronary artery disease, the suggestion that triglyceride levels are relevant to subsequent cardiovascular events in the setting of diabetes remains controversial. This study evaluates the predictive value of serum triglyceride levels on mortality in post-coronary artery bypass graft (CABG) diabetic patients with subsequent analysis by sex. This longitudinal observational study involving a large metropolitan hospital consists of 1,172 diabetic post-CABG patients (792 men and 380 women) with lipid data collected between the years 1982 and 1992. Cox proportional hazards regression models were used to estimate the risk of mortality and cardiac events associated with triglyceride levels in the highest quartile (> 2.90 mmol/l for men and > 3.12 mmol/l for women). Elevated preoperative serum triglyceride values in post-CABG subjects with diabetes were correlated with increased overall mortality (hazard ratio [HR] 1.26, 95% CI 1.00-1.59). The greatest influence of triglyceride levels was observed on overall (1.89, 1.30-2.73) and event-free survival (1.49, 1.06-2.08) in women. High triglyceride values were also modestly related to risk of cardiac events in diabetic men (1.28, 0.99-1.66). These data suggest that increased preoperative triglyceride levels predict increased late mortality and cardiac event risk in diabetic post-CABG patients, more strongly in women than in men.
    Diabetes Care 12/2000; 23(11):1648-53. · 7.74 Impact Factor
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    ABSTRACT: Dyslipidemia is a prevalent condition that affects patients infected with human immunodeficiency virus (HIV) who are receiving antiretroviral therapy. These preliminary recommendations summarize the current understanding in this area and propose guidelines for management. Existing guidelines for the management of dyslipidemia in the general population formed the general basis for our recommendations. Data on the prevalence and treatment of dyslipidemia of HIV-infected patients, implications of treatment-related dyslipidemia in other chronically ill populations, and pharmacokinetic profiles for the available hypolipidemic agents in non-HIV populations were considered. Although the implications of dyslipidemia in this population are not fully known, the frequency, type, and magnitude of lipid alterations in HIV-infected people are expected to result in increased cardiovascular morbidity. We propose that these patients undergo evaluation and treatment on the basis of existing guidelines for dyslipidemia, with the caveat that avoidance of interactions with antiretroviral agents is paramount.
    Clinical Infectious Diseases 12/2000; 31(5):1216-24. · 9.37 Impact Factor
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    ABSTRACT: HDL cholesterol (HDL-C) is an important independent predictor of atherosclerosis, yet the role that HDL-C may play in the prediction of long-term survival after CABG remains unclear. The risk associated with a low HDL-C level in post-CABG men has not been delineated in relation to traditional surgical variables such as the use of arterial conduits, left ventricular function, and extent of disease. We performed a prospective, observational study of 432 men who underwent CABG between 1978 and 1979 in whom preoperative HDL-C values were available. Baseline lipid and lipoprotein values, history of diabetes mellitus and hypertension, left ventricular ejection fraction, extent of disease, and use of internal thoracic arteries were recorded. Hazard ratios (HRs) were determined in the patients with and without a low HDL-C level, which was defined as the lowest HDL-C quartile (HDL-C </=35 mg/dL). After adjustment for age, as well as for baseline metabolic parameters and surgical variables just noted, HDL-C corresponded to both overall (HR 0.40, CI 0.20 to 0.83, P:=0.01) and event-free (HR 0.41, CI 0.24 to 0.70, P:=0.001) survival. Patients with a high HDL-C level (>35 mg/dL) were 50% more likely to survive at 15 years than were patients with low HDL-C level (</=35 mg/dL) (74% versus 57% adjusted survival, respectively; HR 1.72, P:=0.005). In addition, HDL-C showed a strong effect on time-to-event survival such that patients with an HDL-C level of >35 mg/dL were 50% more likely to survive without a subsequent myocardial infarction or revascularization (HR 1.42, P:=0.02). HDL-C is an important predictor of survival in post-CABG patients. In this study of >8500 patient-years of follow-up, HDL-C was the most important metabolic predictor of post-CABG survival. One third fewer patients survive at 15 years if their HDL-C levels are </=35 mg/dL at the time of CABG. The measurement of HDL-C provides a compelling strategy for the identification of high-risk subsets of patients who undergo CABG.
    Circulation 11/2000; 102(19 Suppl 3):III90-4. · 15.20 Impact Factor
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    D L Sprecher, G L Pearce
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    ABSTRACT: The aim of the study was to determine the value of a cluster of metabolic risk factors in predicting mortality after coronary artery bypass surgery (CABG). The "deadly quartet" of metabolic risk factors (i.e., obesity, diabetes, hypertension, and hypertriglyceridemia) has been associated with coronary heart disease in healthy population studies. The expected influence of the cluster on survival in secondary prevention remains untested overall as well as by gender. Patients with lipid profiles undergoing primary isolated CABG (n = 6,428) between 1987 and 1992 were followed a median of eight years. Cox models were used to evaluate all-cause mortality. Metabolic risk factors were incorporated as the sum of deadly quartet risk factors present in each patient (0 to 4). The role of gender as it relates to survival and metabolic risk clusters was also examined. The sum of deadly quartet risk factors showed a significant relationship to mortality as the hazard ratio increased from 1.64 (confidence interval [CI] = 1.34-2.01) for one risk factor to 3.95 (2.73-5.69) for four risk factors. Annualized mortality ranged from 1% per year in patients with no risk factors to 3.3% per year in patients with all four risk factors. Within gender, the hazard ratio associated with four risk factors was 2.58 for men and 13.39 for women. The expected clustering of risk factors was 8% compared to the observed clustering of 10% in men and 21% in women. This cohort showed risk factor clustering beyond that expected due to chance, particularly in women. Even after revascularization, survival is diminished for patients with members of a family of metabolic risk factors at the time of surgery.
    Journal of the American College of Cardiology 11/2000; 36(4):1159-65. · 14.09 Impact Factor
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    ABSTRACT: Previous studies of lipids in adolescent males have shown greater increases in triglycerides and decreases in high-density lipoprotein cholesterol (HDL-C) in white boys compared with black boys, significant correlations between sex hormones and lipids, and complex body mass index (BMI) hormone-lipid associations. Within this frame of reference, we assessed race, BMI, and sex hormones as predictors of lipid parameters in 536 black and white boys recruited from area schools. Black boys were more advanced in puberty than white boys. After adjusting for pubertal stage, estradiol (E2) levels were higher in black boys but free testosterone (T) levels did not differ. Age, pubertal stage, race, BMI, free T, and E2 were entered as explanatory variables for lipids in backward stepwise regression analyses. The BMI and race were retained in every model. Black boys had lower triglycerides and apolipoprotein B (apo B) and higher HDL-C. E2 was inversely associated with total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), apo B, and the LDL-C/HDL-C ratio. Free T was inversely associated with HDL-C and positively associated with apo B. Given the increases in free T and E2 during adolescence and the association of these hormones with both atherogenic and protective lipid parameters, racial differences in E2 could contribute to the more atherogenic lipid profile found in white boys after puberty.
    Metabolism 10/2000; 49(9):1124-9. · 3.10 Impact Factor
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    ABSTRACT: We performed a prospective observational study on 6,602 subjects (94% for 5 years and 34% for 10 to 15 years) who underwent coronary artery bypass graft surgery (CABG) between 1982 and 1992. We examined whether triglyceride concentrations adjusted for other factors (total cholesterol, history of diabetes mellitus, systemic hypertension, left ventricular function, number of coronary arteries significantly narrowed, and use of the internal thoracic arteries) explained total and event-free survival. These analyses were duplicated within gender (1,354 women and 5,248 men). This approach allowed a determination of any gender-related disparities in lipid predictors. Triglycerides in the highest quartile were associated with an increased risk of mortality of 20% (confidence interval [CI] 1.0 to 1.4). Similar risk was seen for event-free survival. Although there was no evidence of gender differences in adjusted survival (p = 0.33), a gender by triglyceride interaction (p = 0.004) indicated that the response to high triglycerides as related to survival did differ by gender. Specifically, women had a dramatically higher risk (hazard ratio [HR] 1.5, CI 1.1 to 2.1) than men (HR 1.1, CI 0.9 to 1. 3). Both men and women did have triglyceride-associated risk with regard to event-free survival (HR in men 1.2, CI 1.1 to 1.4; HR in women 1.4, CI 1.1 to 1.8). Examination of high-density lipoprotein cholesterol in a subcohort did not eliminate the observed triglyceride effects. Thus, triglyceride baseline values are primary determinants (similar to baseline left ventricular function or extent of coronary disease) for long-term total and event-free mortality after CABG in women but not in men.
    The American Journal of Cardiology 09/2000; 86(3):285-8. · 3.21 Impact Factor
  • The American Journal of Cardiology 09/2000; 86(4):455-7. · 3.21 Impact Factor
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    ABSTRACT: A family of extremely reactive electrophiles, isolevuglandins (isoLGs), is generated in vivo by free radical-induced lipid oxidation and rearrangement of endoperoxide intermediates of the isoprostane pathway. Protein adducts of two different oxidized lipids, isoLGE(2) and iso[4]LGE(2), and the corresponding autoantibodies are present in human blood. Western blot analysis of a polyacrylamide gel electrophoresis gel detects several immunoreactive plasma proteins. Only a minor fraction of the isoLG-protein modifications is associated with low density lipoprotein since mean levels were decreased only 20-22% by immunoprecipitation of apolipoprotein B (apoB). Mean levels of both isoLGE(2) and iso[4]LGE(2)-protein adducts in plasma from patients with atherosclerosis (AS) (n=16) or end-stage renal disease (RD) (n=8) are about twice those in healthy individuals (n=25). These elevated levels are not related to variations in age, total cholesterol or apoB. A linear correlation (r=0.79) between plasma isoLGE(2) and iso[4]LGE(2)-protein adduct levels in all 49 individuals is consistent with a common free radical-induced mechanism for the production of both oxidized lipids in vivo. The correlation is even stronger (r=0.86) for patients with AS or RD. That isoLG-protein adduct levels are more strongly correlated with disease than are total cholesterol or apoB suggests an independent defect that results in an abnormally high level of oxidative injury associated with AS and RD.
    Biochimica et Biophysica Acta 06/2000; 1485(2-3):225-35. · 4.66 Impact Factor
  • D L Sprecher
    Cleveland Clinic Journal of Medicine 04/2000; 67(3):169-71. · 3.40 Impact Factor
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    ABSTRACT: A biochemical link between homocysteine (tHcy) and lipoprotein(a) [Lp(a)] related to fibrin binding has been proposed. This hypothesis has not been specifically examined in human subjects. We sought to determine in a clinical setting whether these risk factors would interact to increase coronary artery disease (CAD) risk. We performed a cross-sectional analysis of 750 men and 403 women referred to a preventive cardiology clinic at the Cleveland Clinic Foundation, in whom baseline tHcy and Lp(a) data were available. Logistic regression after adjusting for standard cardiovascular risk factors was used to estimate the relative risk of CAD in patients with an Lp(a) >/=30 mg/dL and a tHcy >/=17 micromol/L. Neither isolated high tHcy (odds ratio [OR]=1.06, P=0.89) nor isolated high Lp(a) (OR=1.15, P=0.60) appeared to be associated with CAD in women. However, strong evidence of an association was seen when both risk factors were present (OR=4.83, P=0.003). Moreover, this increased risk showed evidence of an interactive effect beyond that attributable to either additive or multiplicative effects of tHcy and Lp(a) (P=0.03). In contrast, both elevated tHcy (OR=1.93, P=0. 05) and elevated Lp(a) (OR=1.87, P=0.01) showed evidence of being independent risk factors for CAD in men. The presence of both risk factors in men did not appear to confer additional risk (OR=2.00, P=0.09), even though ORs as high as 12.4 were observed within specific age intervals. Consistent with prior studies, tHcy and Lp(a) are risk factors, either independently or in concert, for CAD in this clinical population. More significantly, we found evidence that when both risk factors were present in women, the associated risk was greater than what would be expected if the 2 risks were simply acting independently. The absence of such an interactive effect in men may be due to the confounding effects of age manifested as "survivor bias." These clinical findings provide insights into the potential roles of both tHcy and Lp(a) in the pathogenesis of atherosclerosis.
    Arteriosclerosis Thrombosis and Vascular Biology 02/2000; 20(2):493-9. · 6.34 Impact Factor
  • D.L. Sprecher, G.L. Pearce
    Journal of the American College of Cardiology 01/2000; 36(4). · 14.09 Impact Factor

Publication Stats

2k Citations
374.55 Total Impact Points

Institutions

  • 1996–2001
    • Cleveland Clinic
      • Department of Cardiology
      Cleveland, OH, United States
  • 1999
    • The Ohio State University
      • Department of Pediatrics
      Columbus, OH, United States
  • 1993–1999
    • Cincinnati Children's Hospital Medical Center
      • • Division of Cardiology
      • • Department of Pediatrics
      Cincinnati, OH, United States
    • Washington University in St. Louis
      • Division of Biostatistics
      San Luis, Missouri, United States
    • University of Michigan
      Ann Arbor, Michigan, United States
  • 1992–1997
    • University of Cincinnati
      • Department of Internal Medicine
      Cincinnati, OH, United States
  • 1993–1994
    • University of Washington Seattle
      • Department of Biostatistics
      Seattle, WA, United States