CLINICAL RESEARCH Clinical Trials

Prospective Serial Evaluationof Myocardial Perfusion and LipidsDuring the First Six Months of Pravastatin TherapyCoronary Artery Disease Regression SinglePhoton Emission Computed Tomography Monitoring TrialRonald G. Schwartz, MD, MS, FACC,* Thomas A. Pearson, MD, PHD, FACC,*Vijay G. Kalaria, MD, FACC,† Maria L. Mackin, CNMT,* Daniel J. Williford, MD, PHD, FACC,*Ashish Awasthi, MD,* Abrar Shah, MD,* Adam Rains, MSC,* Joseph J. Guido, MS*Rochester, New York; and Indianapolis, Indiana

OBJECTIVES This study was designed to assess prospectively changes in serum lipid profile and myocardialperfusion with serial radionuclide single photon emission computed tomography (SPECT)myocardial perfusion imaging (MPI) during the first six months of pravastatin therapy.

BACKGROUND Morbid coronary events occur despite statin therapy and lipid-lowering in patients withcoronary artery disease (CAD). A reliable strategy to identify responders with effectivetreatment from nonresponders on statin therapy before clinical events is needed.

METHODS Rest and stress SPECT MPI and lipids were assessed serially in 25 patients (36% women)with CAD and dyslipidemia during the first six months of pravastatin therapy.

RESULTS Total cholesterol, low-density lipoprotein cholesterol, and triglycerides declined (26%, 32%,and 30%, respectively) by six weeks and remained reduced at six months. Mean stressperfusion defect (summed stress score [SSS]) was severe (13.3 � 6.0) at baseline, showed nochange at six weeks, and improved significantly at six months (10.3 � 7.3, p � 0.01). Thesix-month study SSS improved in 11 (48%) patients, was unchanged in 10 (43%) patients,and worsened in 2 (9%) patients. Changes in lipid levels did not reliably predict changes inmyocardial perfusion at six weeks or six months in this small pilot study.

CONCLUSIONS Serial SPECT MPI demonstrated improved stress myocardial perfusion in 48% of patientstreated for six months with pravastatin. Time course of improved myocardial perfusion duringpravastatin therapy is delayed compared to lipids. Direction and magnitude of changes in themyocardial perfusion vary and do not correlate closely with improvements in lipids. (J AmColl Cardiol 2003;42:600–10) © 2003 by the American College of Cardiology Foundation

Statins modify serum lipid profiles favorably and reducecoronary events substantially. Despite the documented ef-fectiveness of statins, annual cardiovascular event rates instatin-treated patients are nontrivial: 1.7% to 2.5% inprimary prevention trials (1,2) and 6.4% to 7.8% in second-ary prevention trials (3–6). Identifying treated patients witheffectively lowered cholesterol levels who remain at risk ofcoronary events remains problematic.

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The complexity and pleiotropism (7) of therapeutic re-sponses to statin therapy suggest the potential value of

monitoring strategies more predictive than the cholesterolprofile to determine effective therapeutic response beforeclinical events. An ideally predictive modality would facili-tate timely adjustment of therapeutic strategy to yieldimproved clinical outcomes in nonresponsive patients. Ra-dionuclide single photon emission computed tomography(SPECT) and positron emission computed tomography(PET) myocardial perfusion imaging (MPI) provides riskassessments in patients with known or suspected coronaryartery disease (CAD) incremental to clinical, exercise,and/or coronary arteriographic variables (8–14). Abnormal-ities of stress-induced coronary vasomotion identify site-specific location of stenosis development and predict morbidcoronary events (15). Effective cholesterol-lowering im-proves coronary endothelium-dependent vasodilation andmyocardial perfusion by invasive measurement with Dopp-ler flow wire (16) and by PET and SPECT radionuclideMPI (13,17–26), as well as increasing coronary arterydiameter by contrast arteriography (13,27).

Improvements in perfusion accompanying cholesterol-lowering with serial radionuclide MPI have been reportedfrom 30 days (20) to 5 years (13). However, the incidence

From the *Cardiology Unit, Department of Medicine; Division of NuclearMedicine, Department of Diagnostic Radiology; and the Department of Communityand Preventive Medicine, University of Rochester School of Medicine and Dentistry,Rochester, New York; and the †Krannert Institute of Cardiology, Department ofMedicine, Indiana University, Indianapolis, Indiana. The study was funded by aresearch grant from Bristol-Myers Squibb Company. This work was presented in partat the 50th Annual Scientific Session of the American College of Cardiology, March2001, Orlando, Florida.

Manuscript received November 5, 2002; revised manuscript received January 30,2003, accepted March 12, 2003.

Journal of the American College of Cardiology Vol. 42, No. 4, 2003© 2003 by the American College of Cardiology Foundation ISSN 0735-1097/03/$30.00Published by Elsevier Inc. doi:10.1016/S0735-1097(03)00767-8

and time course of serial changes in myocardial perfusion,relative to changes in lipid profile and clinical course, remainunclear. One prior PET MPI study observed that statin-induced augmentation of coronary flow reserve at sixmonths by PET MPI is delayed compared to its lipid-lowering effects at two months (25). Given the establishedlipid-lowering effect of pravastatin by six weeks and itstherapeutic effectiveness in reducing coronary events as earlyas six months in the West of Scotland trial in men (1), andin women in the Cholesterol And Recurrent Events trial(3), the present study was designed to compare the timecourse of changes in lipid levels and stress perfusion bySPECT MPI following the initiation of pravastatin therapy.

METHODS

Patient selection. Twenty-five dyslipidemic (total choles-terol [TC] �200 mg/dl, low-density lipoprotein [LDL]�130 mg/dl, or TC:high-density lipoprotein [HDL] �4)patients with clinical CAD and stress-induced myocardialperfusion defects were enrolled. Patients were excluded ifthey took statin therapy during the previous two months.With approval of the Research Subjects Review Board, theinformed consent process was performed for all patients.Therapeutic intervention, compliance, and follow-up.Pravastatin 40 mg qhs for six months was initiated andcompliance was assessed by monthly pill counts. Follow-upclinical evaluation at six weeks and six months was per-formed with lipid levels, liver function tests, and SPECTMPI. Consideration of fibrate and niacin therapy was givento patients with TC:HDL �4 at six weeks. All patientswere counseled closely with regard to lifestyle modificationincluding smoking cessation, calorie-constrained diet toachieve ideal body weight with �30% fat calories, lowcholesterol, and at least 30 min aerobic exercise most days ofthe week.Stress testing and pre-testing medication management.Medication usage was reviewed and beta-blockers, calciumantagonists, nitrates, and angiotensin-converting enzymeinhibitors were routinely held to standard therapeutictrough levels before stress testing. Patients were instructedto avoid caffeine consumption for 24 h before the stress test.Exercise and adenosine stress testing was performed in 11

and 12 patients, respectively. In all but two patients thestress testing modality was maintained for all serial imaging(baseline, six weeks, and six months). Rate-pressure productand Duke treadmill exercise scores were calculated in the 11patients who underwent exercise testing.SPECT perfusion imaging and interpretation. Routinedual tracer (rest-thallium-201, exercise, or adenosine stressTc-99m-sestamibi) SPECT MPI was performed using adual-head SPECT DST camera (GE/SMV Medical Sys-tems, Milwaukee, Wisconsin) with 60-s acquisitions perstop for 32 total stops (16 stops per head) with low energyhigh resolution collimators. Rest and stress perfusion imageswere processed on MIRAGE PC-based software (SegamiCorp., Ellicott City, Maryland). Vertical and horizontalspatial filtering of the back-projected data was performedwith a Butterworth low pass filter (frequency cut-off � 0.4,order � 6, size � 15). Consensus interpretation usingquantitative analysis of SPECT MPI data with visualover-reading by three readers was employed. Semiquantita-tive regional scoring was performed for stress and restimages using the Cedars method (9,12), which employs afive-point scale from normal (0) to absent tracer (4).Semiquantitative regional scores were recorded in theNuclear Cardiology Database System using PC-based Vi-sual Foxpro (Microsoft Corp., Seattle, Washington) withautomated calculation of summed perfusion scores (summedrest score [SRS], summed stress score [SSS], summeddifference score [SDS]). Differences in summed perfusionscores (SSS, SRS, and SDS) from baseline to eachfollow-up period were rated as previously described (12)(�3 � “improved,” ��3 to �3 � “no change,” ��3 �“worse”). Left ventricular (LV) volume and ejection frac-tions were obtained from the Vision PowerStation usingMultiDim (GE/SMV Medical Systems) with the use ofno-acquisition zoom, 2.5:1 intraprocessing zoom, and aMetz Filter (3.5 full width half maximum, order 8 resultingin a 2.7-mm pixel size) as validated in our laboratory.

To verify scintigraphic results, blinded visual analysis ofperfusion images and automated quantitative analysis of thepercent of LV hypoperfusion by defect score and globalextent on three-dimenstional topograms was performedusing the Yale Wackers-Liu CQ method (28) (EclipseSystems, Branford, Connecticut). The direction and mag-nitude of changes in the myocardial perfusion and lipidprofile components were noted for each patient and for theentire study cohort.Statistical methods. The existence of changes in lipids(TC, HDL, TC:HDL, LDL, triglycerides), scan readings(SSS, SRS, SDS), and the percent of LV hypoperfusion ofdefect size and global defect extent (Wackers-Liu CQmethod) across the three time periods (baseline, six weeks,and six months) of the study was evaluated by analysis ofvariance. Values found by analysis of variance to havechanged significantly within the study period were subjectedto pairwise comparison of means between each time periodusing the paired t test. The power of the analysis of variance

Abbreviations and AcronymsCAD � coronary artery diseaseHDL � high-density lipoproteinLDL � low-density lipoproteinLV � left ventricularMPI � myocardial perfusion imagingPET � positron emission tomographySDS � summed difference scoreSPECT � single photon emission computed tomographySRS � summed rest scoreSSS � summed stress scoreTC � total cholesterol

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and paired t tests to correctly identify deviations from thenull hypothesis was determined post-hoc using the methodsdescribed by Zar (29). For all analyses, the significance levelwas set at 5% and dropouts were excluded from consider-ation. All analyses were conducted using SAS/STAT forWindows (version 8.2, SAS Institute Inc., Cary, NorthCarolina).

RESULTS

Preliminary evaluation of lipid, scan, and perfusion values byanalysis of variance identified statistically significant (p �0.05) changes in the following measures during the studyperiod: SSS, TC, HDL, LDL, triglycerides, quantitativepercent of the LV hypoperfusion of stress defect score,global extent, and TC:HDL ratio. On the basis offollow-up analysis by paired t test, significant changes ineach measure were noted as follows: TC, LDL, andtriglycerides changed during the first time period (baselineto six weeks); SSS, quantitative defect extent, and HDLchanged during the second time period (six weeks to sixmonths); and TC:HDL changed during both time periods.Clinical characteristics of the patient population. Of the25 patients (9 women; 36%) who enrolled in the trial, 23(92%) completed the entire study. Two study dropoutsexcluded from analysis included a man referred for coronaryartery bypass graft surgery because of decreased perfusion atsix weeks and a woman with improved perfusion at sixweeks who failed subsequent follow-up. Baseline clinicalcharacteristics of the 23 patients completing the study aresummarized in Table 1. Eleven of the 23 recruited patientshad a new diagnosis of CAD. Medications taken at base-line, six weeks, and six months are listed in Table 2. Withthe exception of three patients who received angiotensin-converting enzyme inhibitors and five patients who receivedniacin between six weeks and six months, most medicationchanges were completed before the six-week visit.Compliance and tolerance of pravastatin. On the basis ofpill counts, mean compliance with the pravastatin regimenwas �95% (minimum 91.1%). No patient experiencedsignificant elevations (�2 � upper normal limit) in liverfunction tests, or reported myalgia, fatigue, or other adverseeffects attributable to pravastatin.Stress testing. Eleven of the 23 study patients underwentprovocative stress testing with an exercise protocol. Anginaduring exercise tolerance testing (ETT) was reported bythree patients at baseline, one patient at six weeks, and noneat six months. Group mean rate-pressure product at baseline(28,222 � 4,752) and Duke treadmill exercise score (0.14 �10.91) were unchanged at six weeks and six months.Lipid profile and SPECT MPI during pravastatin treat-ment. Lipid profile, the number of patients actively smok-ing and with hypertension, and SPECT MPI values at eachtime period are presented in Table 3. Statistically significantreductions were noted at six weeks for LDL (32%), TC(26%), and triglycerides (30%), which persisted at six

months. Statistically significant changes were also noted atsix months for HDL (15% increase), SSS (23% decrease),SDS (40% decrease), and quantitative defect size andtopographic extent percent of LV hypoperfusion (35%decrease) (Figs. 1D to 2B), with no change at six weeks.The TC:HDL declined 25% from baseline to six weeks anddeclined 32% from six weeks to six months. No significantchanges in SRS, quantitative resting perfusion defect size orextent, left ventricular ejection fraction, or left ventricularend-systolic volume index were noted at six weeks or sixmonths (Table 3).

Average baseline SSS was severe (13.3 � 6; mean � SD)and declined to a moderate-average score (10.3 � 7.3) at sixmonths. Of the 23 patients completing the study, SSSdeclined in 11 (48%) patients, which included completenormalization (�4) in 5 (22%) patients; SSS remained

Table 1. Baseline Clinical Characteristics of 23 PatientsCompleting the Study

Coronary risk factorsAge, 59.9 � 9.5 yrsHistory of MI, n � 9Diabetes, n � 5Hypertension, n � 12LDL �130 mg/dl, n � 11; TC �200 mg/dl, n � 17;

TC:HDL �4.0 mg/dl, n � 19Low HDL (�35 mg/dl in men or �45 mg/dl in women mg/dl),

n � 14Smoking: history of smoking, n � 10; active smokers, n � 5Number of coronary risk factors � 4.7 � 1.5

Indications for index SPECT MPI studyChest pain or exertional dyspnea, n � 10Postinfarction risk stratification, n � 6Hemodynamic assessment of known coronary artery disease, n � 3Evaluation of an abnormal ECG, n � 2Preoperative risk stratification, n � 2

Coronary angiography, n � 8Single-vessel disease, n � 4Multivessel disease, n � 4

2-vessel disease, n � 23-vessel disease, n � 2

Coronary end points during study of the original 25-patient cohortMI, n � 1Coronary artery bypass graft surgery, n � 1Unstable angina, PCI, cardiac death, n � 0

ECG � electrocardiogram; HDL � high-density lipoprotein; LDL � low-densitylipoprotein; MI � myocardial infarction; MPI � myocardial perfusion imaging;PCI � percutaneous coronary intervention; SPECT � single photon emissioncomputed tomography; TC � total cholesterol.

Table 2. Medications Taken at Baseline, Six Weeks, andSix Months

Medication Baseline 6 Weeks 6 Months

Aspirin 15 21 22Beta-blocker 12 18 19ACE inhibitor 7 8 11A2 receptor blocker 0 1 1Calcium blocker 4 4 3Estrogen 3 3 3Nitrate 4 2 2Niacin 0 1 6

ACE � angiotensin-converting enzyme.

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unchanged in 10 (43%) patients and increased in 2 (9%)patients (Table 4). Four of 23 (17%) patients had worse SSSat six weeks than at six months. One of these four patientshad a history of prior Q-wave myocardial infarction anddeveloped recurrent infarction with deepening of Q wavesin two of the inferior electrocardiographic leads before sixweeks of therapy with pravastatin. Asymptomatic progres-sion of the scan defects was noted in the other three patientsat six weeks. Six-month scans of these four patients revealedimprovement in one patient, deterioration in one patient,and no change in two patients as compared with six-weekscans. The resting study was unchanged in 12 patients(52%), improved in 6 (26%) patients, and worse in 4 (17%)patients. The SDS was better in 14 (61%) patients, un-changed in 5 (22%) patients, and worse in 4 (17%) patients(Table 4).

The direction and magnitude of changes in the myocar-dial perfusion were variable and did not correlate withimprovement of the lipid profile. Twenty-one of 23 patientsshowed improved LDL levels at six months; however, stressperfusion improved (reduced SSS �3) in only 9 of thesepatients. Of two patients in the study who failed to show asignificant reduction of LDL cholesterol by six months,stress perfusion improved significantly (reduced SSS �3) ineach. Responses of SSS to pravastatin therapy with eitherexercise or adenosine stress were similar.Other medical therapy and changes of myocardial perfu-sion. Medication changes between six weeks and sixmonths did not correlate with perfusion changes observed.Of the three patients started on angiotensin-convertingenzyme inhibitor therapy, one patient showed improved

SSS, one patient worsened, and one patient remainedunchanged. The HDL increased at six months, but not atsix weeks, potentially because of the addition of niacin aftersix weeks in five patients. However, SSS improved in two ofthese patients and remained unchanged in the other three.Thus, niacin-associated improvement in HDL did notaccount for all the changes in SSS between six weeks and sixmonths.

DISCUSSION

Our laboratory first reported statin-induced improvementsin stress myocardial perfusion by SPECT MPI in 1997 (17)following seminal reports of similar improvements withcholesterol-lowering therapy by PET MPI by Gould et al.(13,18) and Czernin et al. (19). Improvements in radionu-clide MPI with lipid-lowering, including lifestyle changesand statins, have subsequently been confirmed indepen-dently by both PET (20,24–26) and SPECT MPI (21,23).Assessment of treatment response to statins by cholesterollevels appears inadequate, as up to 7.8% of patients withimproved lipids on statin therapy experience coronary eventsin randomized controlled trials (1–6). Beyond cholesterol-lowering, radionuclide tomographic MPI may identify ef-fective statin treatment response associated with improve-ment of abnormalities of endothelial function associatedwith dyslipidemia or CAD (15–26,30,31) as recently re-viewed (22).

The current study is the first prospective serial monitor-ing trial using SPECT MPI to assess both early and latechanges in myocardial perfusion and the lipid profile duringthe first six months of statin therapy. The principal findingof this study is pravastatin reduced abnormalities of stressperfusion (SSS, SDS, quantitative defect extent) by radio-nuclide SPECT MPI at six months but not six weeks incompliant dyslipidemic patients with CAD. In contrast,pravastatin reduced serum levels of TC, LDL cholesterol,and triglycerides by six weeks, and these reductions persistedat similar levels at six months. Despite a 32% reduction inLDL for the study group, the direction and magnitude ofchanges in stress myocardial perfusion varied widely. Nochange of group mean resting perfusion (SRS) was observedduring the study, similar to prior SPECT (21) and PET(25) monitoring studies during statin therapy. Differences inMPI technique, study population, time course, degree ofresting endothelial dysfunction, definition, or degree ofdyslipidemia may account for the lack of alteration of restingperfusion observed in our study. As expected, no changes ofleft ventricular ejection fraction, end-diastolic volume index,or end-systolic volume index were observed during thissix-month study.

The results contribute to our current understanding that:1) scan findings parallel the time course of earliest docu-mented coronary event reduction in the randomized clinicaltrials by pravastatin (1,3), rather than the earlier reductionof lipid changes that occurred at six weeks; 2) normalization

Table 3. Single Photon Emission Computed TomographyMyocardial Perfusion Imaging, Lipid Profile Values, andCoronary Risk Factors During Pravastatin Therapy

Baseline 6 Weeks 6 Months

TC (mg/dl) 220 � 37 163 � 23* 171 � 27*HDL cholesterol (mg/dl) 41 � 12 42 � 11 47 � 11*†TC:HDL ratio 5.60 � 1.30 4.18 � 1.08* 3.81 � 0.95*†LDL cholesterol (mg/dl) 134 � 31 91 � 18* 96 � 23*Triglycerides (mg/dl) 232 � 128 162 � 59* 154 � 68*SSS 13.3 � 6.0 12.3 � 7.2 10.3 � 7.3*SRS 5.0 � 4.1 5.8 � 4.6 5.3 � 4.7SDS 8.3 � 4.6 6.5 � 7.2 5.0 � 8.0*Extent (% LV) hypoperfusion 25.5 � 13.7 24.5 � 14.1 16.6 � 13.8*LV volume and function

LVEDVI (ml/m2) 84 � 22 86 � 21 81 � 18LVESVI (ml/m2) 40 � 16 42 � 14 38 � 13LVSVI (ml/m2) 44 � 10 44 � 10 43 � 8LVEF (%) 54 � 8 52 � 8 53 � 7Active smokers (n) 5 3 3SBP �140 mm Hg or

DBP �90 mm Hg (n)7 5 6

*Significant t test (p � 0.05) for comparison to baseline value (mean � SD);†significant t test (p � 0.05) for comparison to 6-week value (mean � SD).

DBP � diastolic blood pressure; LV � left ventricular; LVEDVI � left ventricularend-diastolic volume index; LVEF � left ventricular ejection fraction; LVESVI �left ventricular end-systolic volume index; LVSVI � left ventricular stroke volumeindex; SBP � systolic blood pressure; SDS � summed difference score; SRS �summed rest score; SSS � summed stress score. Other abbreviations as in Table 1.

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of stress scans, which is known to be associated withimproved prognosis during anti-ischemic therapy (32,33),and an extremely low rate of subsequent coronary eventsreported for patients with normal scans (8,9,11,12,14,34),

was observed in 22% of patients on statin therapy; and 3)changes in the direction and magnitude of serum lipidslevels did not closely parallel the improvement of stressperfusion in individual patients.

Figure 1. (A to C) Single photon emission computed tomography myocardial perfusion imaging orthogonal plane images before pravastatin therapy(baseline), at six weeks, and at six months of pravastatin therapy in a typical patient with reduced summed stress score by six months. Consistent withrandomized controlled trials, pravastatin 40 mg was administered on a non-dose titrated basis. Stress perfusion defect size declined in 11 (48%) and wasstable in 10 (43%) of 23 patients completing the trial. Continued on next page.

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Our findings confirm a prior PET MPI study showingstatin-induced improvement of stress perfusion at sixmonths follows earlier lipid-lowering at two months andappeared unrelated to the amount of lipid-lowering (25).Statin-induced upregulation of endothelial nitric oxide syn-thase by Rho GTPase is an important mechanism ofimproved endothelial function and myocardial perfusionregulated downstream from cholesterol-lowering HMG-

CoA reductase pathway (35). Additionally, numerous pleio-tropic effects of statins appear to contribute to their thera-peutic effectiveness (7,36).Potential study limitations. Medications in addition topravastatin after the baseline SPECT MPI study mighthave contributed to the scan changes; however, we did notobserve any response trend in patients with altered medica-tion regimen. Only modest absolute changes in myocardial

Figure 1 Continued on next page.

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perfusion were noted during this six-month study. How-ever, these findings are consistent with prior reports ofdisproportionately greater effects of statin therapy on myo-cardial perfusion and cardiac events than on modest regres-sion of coronary stenoses in randomized arteriographic trials(13). Because of limited sample size, this study may haveinsufficient power to detect minor or short-term changes inSPECT MPI variables and their correlation with serumlipid levels. Post-hoc analyses indicate a power in excess of

80% for all changes in lipid and scan values (baselinecompared to six months) with the exception of HDL (71%).Lack of placebo arm is a potential weakness, but such trialdesign is considered unethical in the current era of docu-mented effectiveness of statins in patients with CAD(2–4,6). Open-label study design might lead to scan inter-pretation bias; however, re-analyses of scans without knowl-edge of their chronologic order (data not shown) andautomated quantitative analyses (Figs. 1B and 2B) have

Figure 1 Continued on next page.

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Figure 1 Continued. (D) Automated quantitative analyses of defect (percent of left ventricular hypoperfusion) size (left images) and global extent (right images) at baseline, sixweeks, and six months of pravastatin therapy. Quantitative analyses verified improved average stress perfusion by six months in the study population.

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Figure 2. (A) Single photon emission computed tomography (SPECT) summed stress score (SSS) and summed difference score (SDS) (SDS � SSS � summed rest score [SRS]) of myocardial perfusionabnormalities at baseline and six months are compared. Significant reductions in these perfusion indices were observed. In contrast, SSS was not reduced at six weeks. The SRS did not change during thestudy (see text). Lines track individual patient values from baseline to the six-month study. Continued on next page.

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confirmed the results. Serial changes of high sensitivityC-reactive protein and other inflammatory markers poten-tially modulated by statins (36) were not assessed in thecurrent study.Conclusions. In compliant dyslipidemic patients with ab-normal baseline myocardial perfusion by SPECT MPI,pravastatin therapy improved stress perfusion in 48% of thestudy patients by six months but not by six weeks. Divergentresponses to pravastatin of lipid and scintigraphic parame-ters were observed and variability of responses was substan-tial. Scan improvement did not correlate with the magni-tude of LDL reduction in this small pilot study.

Serial monitoring of stress radionuclide PET andSPECT perfusion abnormalities during pravastatin therapymay identify substantial variability in the presence andmagnitude of therapeutic response not reflected by theserum lipid response. Whether patients who fail to improvestress myocardial perfusion despite appropriate lipid-

lowering on statin therapy are at increased risk of coronaryevents is not yet known. The results of the current studysupport longer term prospective investigation of serialchanges in lipids and radionuclide MPI during statintherapy and correlation with clinical outcomes to assess thetime course and characteristics of effective therapeutic re-sponse. This combined lipid and radionuclide tomographicperfusion-guided approach may improve assessment of theresidual risk on statin therapy and facilitate optimal utiliza-tion of medical and revascularization therapies.

AcknowledgmentsWe gratefully acknowledge the dedicated and skillful careand coordination efforts of Pat Grego, ANP, and KrisKremer, RN, who made this study possible.

Reprint requests and correspondence: Dr. Ronald G. Schwartz,University of Rochester Medical Center, Cardiology Unit, Box679, 601 Elmwood Avenue, Rochester, New York 14642-8679.E-mail: Ronald_Schwartz@URMC.Rochester.edu.

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Figure 2 Continued. (B) Automated analyses of the stress SPECT myocardial perfusion defect size and topographic extent quantified by percent of LVhypoperfusion, using the Yale Wackers-Liu software program. Similar to the SSS, no differences were found between baseline and six-week studies (notshown). Lines track individual patient values from baseline to the six-month study.

Table 4. Change in Single Photon Emission ComputedTomography Perfusion: Baseline vs. Six Month Scans

Better(>3)

Same(<3 and >�3)

Worse(<�3)

� SSS 11 (48%)* 10 (43%) 2 (9%)� SRS 6 (26%) 12 (52%) 5 (22%)� SDS 14 (61%) 5 (22%) 4 (17%)

� summed perfusion scores � (baseline scan) � (6-month scan). *SSS normalized(�4) in 5 (22%) patients.

Abbreviations as in Table 3.

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