C-Reactive Protein is Not Associated C-Reactive Protein is Not Associated with Cardiovascular Events with Cardiovascular Events

Following Percutaneous Coronary Following Percutaneous Coronary Intervention with Drug-Eluting Intervention with Drug-Eluting

Stents at 3-Year Follow-UpStents at 3-Year Follow-Up

Tina L Pinto Slottow MD, Nicholas Hanna MD, Daniel Steinberg MD, Probal Tina L Pinto Slottow MD, Nicholas Hanna MD, Daniel Steinberg MD, Probal Roy MD, Zhenyi Xue BS, Kimberly Kaneshige BS, Rebecca Torguson MS, Roy MD, Zhenyi Xue BS, Kimberly Kaneshige BS, Rebecca Torguson MS,

Joseph Lindsay MD, Augusto Pichard MD, Lowell Satler MD, William Suddath Joseph Lindsay MD, Augusto Pichard MD, Lowell Satler MD, William Suddath MD, Kenneth Kent MD PhD, and Ron Waksman, MDMD, Kenneth Kent MD PhD, and Ron Waksman, MD

Division of Cardiology, Washington Hospital Center, Washington, DC, USADivision of Cardiology, Washington Hospital Center, Washington, DC, USA

IntroductionIntroduction Inflammatory mechanisms play a central role in Inflammatory mechanisms play a central role in

the pathogenesis of atherosclerosis. the pathogenesis of atherosclerosis.

Elevated hsCRP is a marker of inflammation that Elevated hsCRP is a marker of inflammation that has been shown to be associated with adverse has been shown to be associated with adverse cardiovascular events. cardiovascular events.

Evaluation of the relationship between hsCRP Evaluation of the relationship between hsCRP and clinical outcomes following PCI have and clinical outcomes following PCI have demonstrated mixed results.demonstrated mixed results.

The goal of this study was to extend prior The goal of this study was to extend prior observations by examining if baseline observations by examining if baseline

hsCRP is correlated with cardiovascular hsCRP is correlated with cardiovascular events following PCI with DES. events following PCI with DES.

Goal of studyGoal of study

HypothesisHypothesis

Elevated hsCRP would not be associated Elevated hsCRP would not be associated with increased incidence of cardiac death, with increased incidence of cardiac death,

myocardial infarction, or target vessel myocardial infarction, or target vessel revascularization in the DES era.revascularization in the DES era.

MethodsMethods

Retrospective analysis of 1515 consecutive Retrospective analysis of 1515 consecutive patients who underwent unrestricted PCI patients who underwent unrestricted PCI with ≥1 DES between April 2003 and with ≥1 DES between April 2003 and January 2006.January 2006.

Stratified by baseline hsCRP levels that Stratified by baseline hsCRP levels that were measured prior to stent implantation.were measured prior to stent implantation.

MethodsMethods

353 patients had a hsCRP <1.353 patients had a hsCRP <1.

439 between 1 and 3.439 between 1 and 3.

461 between 3 and 10.461 between 3 and 10.

262 greater than 10.262 greater than 10.

MethodsMethods

Incidence of the following was examined Incidence of the following was examined up to 3 years following PCI:up to 3 years following PCI: Cardiac MortalityCardiac Mortality

Myocardial Infarction (MI)Myocardial Infarction (MI)

Target Vessel Revascularization (TVR)Target Vessel Revascularization (TVR)

Patient characteristics stratified by hsCRP levelsPatient characteristics stratified by hsCRP levels

0.10921.0±7.021.1±6.820.2±6.220.3±6.7Stent length (mm)

0.2633.0±0.83.0±0.43.0±0.83.0±0.3Stent diameter (mm)

0.4772.1±3.51.8±0.91.9±2.01.8±1.3Lesions treated (number)

0.3152.1±0.81.9±0.81.9±0.91.9±0.9Diseased vessels (number)

p valuen=230n=400n=406n=305Angiographic characteristics

0.734231 (97.5)396 (98.5)414 (98.6)318 (98.1)Statin use

<0.00160 (23.2)48 (11.3)21 (4.6)16 (4.8)MI during admission

<0.00158 (22.2)59 (13.6)34 (7.4)24 (6.8)History of CRI

<0.00156 (23.1)58 (14)49 (11.3)37 (10.9)History of CHF

<0.00150 (19.1)95 (21.6)64 (13.9)31 (8.8)Current smoker

0.125221 (84.4)393 (90.1)409 (89.1)312 (88.6)Hypercholesterolemia

0.01103 (39.6)151 (34.7)134 (29.4)100 (28.6)Diabetes mellitus

0.642219 (83.6)365 (83.1)376 (81.9)282 (80.1)Hypertension

0.06867.4±11.865.1±11.265.9±11.065.8±11.1Age (years)

<0.001146 (55.7)274 (62.4)337 (73.1)279 (79)Male

<0.00151.9±83.35.5±2.01.9±0.60.6±0.3Baseline hsCRP

p valuen=262n=439n=461n=353Patient Characteristics, n (%)

≥103 to <101 to <3<1hsCRP

Cardiac deathCardiac death

Myocardial infarctionMyocardial infarction

Target Vessel Revascularization Target Vessel Revascularization

ResultsResults

There was a higher incidence of all-cause There was a higher incidence of all-cause mortality in the hsCRP>10 group compared to mortality in the hsCRP>10 group compared to the other groups that was noted at 6 month the other groups that was noted at 6 month follow-up and persisted to 3 year follow-up.follow-up and persisted to 3 year follow-up.

This mortality difference remained even This mortality difference remained even following adjustment for the differences in following adjustment for the differences in baseline characteristics.baseline characteristics.

All-cause mortalityAll-cause mortality

DiscussionDiscussion

Baseline hsCRP is not independently associated Baseline hsCRP is not independently associated with increased risk of cardiovascular events with increased risk of cardiovascular events following intervention at 3 year follow-up. following intervention at 3 year follow-up.

As found in other evaluations of patient groups As found in other evaluations of patient groups with very elevated hsCRP, comorbidities were with very elevated hsCRP, comorbidities were more common in the CRP>10 group. more common in the CRP>10 group.

DiscussionDiscussion

The result of this analysis differs from some The result of this analysis differs from some prior studies that demonstrated differences in prior studies that demonstrated differences in cardiovascular outcomes on hsCRP levels. cardiovascular outcomes on hsCRP levels.

Nonetheless, there are other evaluations that Nonetheless, there are other evaluations that correspond with the findings in this study.correspond with the findings in this study.

DiscussionDiscussion CAPTURE trialCAPTURE trial

reported a high incidence of death and MIreported a high incidence of death and MI

broad assignment of patients to either hsCRP positive broad assignment of patients to either hsCRP positive or hsCRP negative groupsor hsCRP negative groups

neither this, nor other smaller studies, have neither this, nor other smaller studies, have associated hsCRP with the need for repeat associated hsCRP with the need for repeat revascularization, which was one of the primary revascularization, which was one of the primary endpoints in this study.endpoints in this study.

DiscussionDiscussion

Several studies that have reported no Several studies that have reported no association with hsCRP levels and restenosis.association with hsCRP levels and restenosis.

Rittersma et al and Gomma et al found no Rittersma et al and Gomma et al found no statistically significant association with pre-statistically significant association with pre-procedural hsCRP levels and angiographic procedural hsCRP levels and angiographic restenosis at 6 months.restenosis at 6 months. patient population was predominately composed of patient population was predominately composed of

those with stable angina.those with stable angina.

Drug-Eluting StentsDrug-Eluting Stents

One of the main differences between this One of the main differences between this analysis and those preceding. analysis and those preceding.

In the largest studies, only 40% of the de In the largest studies, only 40% of the de Winter et al population required PCI, while Winter et al population required PCI, while Dibra et al had only 23% of their subjects Dibra et al had only 23% of their subjects receiving DES.receiving DES.

Drug-Eluting StentsDrug-Eluting Stents

Several studies have compared DES to BMS in Several studies have compared DES to BMS in the setting of analyzing the prognostic value of the setting of analyzing the prognostic value of hsCRP. hsCRP.

Gibson et al is the largest study (n=741) which Gibson et al is the largest study (n=741) which included three arms comparing BMS to two different included three arms comparing BMS to two different DES individually and as a group. Among the DES individually and as a group. Among the moderate to high risk patients, DES implantation was moderate to high risk patients, DES implantation was associated with reductions in hsCRP and troponin associated with reductions in hsCRP and troponin level. level.

DiscussionDiscussion

The inflammatory process leading to The inflammatory process leading to plaque growth and rupture differs from the plaque growth and rupture differs from the healing inflammatory process after PCI.healing inflammatory process after PCI.

This may trigger strong inflammatory This may trigger strong inflammatory response and confound the utility of hsCRP response and confound the utility of hsCRP as a dependable marker of future events. as a dependable marker of future events.

StatinsStatins

Treatment with statins significantly lowers Treatment with statins significantly lowers hsCRP concentrations independent of their hsCRP concentrations independent of their effects on serum lipids. effects on serum lipids.

Widespread use of statins is sited in Widespread use of statins is sited in multiple studies that compare DES and multiple studies that compare DES and BMS as a possible contributor to improving BMS as a possible contributor to improving outcomes.outcomes.

StatinsStatins

It could be speculated that the high prevalence It could be speculated that the high prevalence of statin use diminished the potential predictive of statin use diminished the potential predictive value of the hsCRP level. value of the hsCRP level.

These findings have important therapeutic These findings have important therapeutic implications towards understanding outcomes implications towards understanding outcomes after PCI.after PCI.

Further studies would be needed to deduce if Further studies would be needed to deduce if baseline hsCRP has any utility in the DES era.baseline hsCRP has any utility in the DES era.

LimitationsLimitations

Non-randomized retrospective analysis, and as Non-randomized retrospective analysis, and as such it is possible that both identified and such it is possible that both identified and unidentified confounders may have influenced unidentified confounders may have influenced the outcomes. the outcomes.

Type of stents used.Type of stents used.

Size of population.Size of population.

AcknowledgementsAcknowledgements

Dr. Ron WaksmanDr. Ron Waksman

Dr. Tina Pinto SlottowDr. Tina Pinto Slottow

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