An anti-inflammatory approach to ASCVD prevention · HsCRP: estimating risk7 Strong evidence hsCRP associated with CHD events RR (95% CI): 1.58 (1.37-1.83) for incidence of CHD in

An anti-inflammatory approach to ASCVD prevention

DR. SCOTT A. COON, PHARMD, BCPS, BCACP

[email protected]

OCTOBER 2018

Conflicts of Interest

No conflicts of interest

Learning Objectives

1. Comprehend the rational for use of non-lipid, inflammatory biomarkers to guide ASCVD risk reduction therapy

2. Describe the relationship between inflammatory biomarker high-sensitivity C-reactive protein (hsCRP) and the incidence of cardiovascular events

3. Understand the anti-inflammatory effects of statins and integrate concepts of inflammatory biomarker theory into primary and secondary ASCVD risk reduction therapy

4. Evaluate the safety/efficacy new and emerging anti-inflammatory ASCVD risk reduction therapies, including the interleukin1-beta inhibitor canakinumab

Flow

• Atherosclerosis and inflammation

• Inflammatory modulators and acute phase reactants

• REVERSAL

• JUPITER & HOPE-3

• PROVE IT

• Meta-analysis

High sensitivity CRP

Background Statins &hsCRP

Canakinumab Conclusions

• Clinical utility

• Relationship with LDL

• ASCVD prevention guidelines

• Interleukin-1β

• CANTOS trial

• Emerging inflammatory modulating ASCVD therapies

• Use of hsCRP to guide treatment decision-making and ASCVD lowering therapy

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AtherosclerosisPATHOPHYSIOLOGY AND INFLAMMATION

Pathophysiology1

Lesions in large-medium sized elastic and muscular arteries accumulate fibrous elements and lipid debris

Not a simple plumbing issue

Immune process

Monocyte maturation to macrophages within atherosclerotic plaques

Signaling cascade, pro-inflammatory cytokines, adhesion molecules

Stimulated production of acute phase reactants

Atherosclerosis Progression

Hyperlipidemia promotes pro-inflammatory state within intimal layer

Modified lipoproteins and oxidized phospholipids assist in the maturation of monocytes to macrophages

Macrophages phagocytize lipoproteins formingfoam cells, inflammation amplified

swollen macrophage filled with lipid inclusions

Drivers of Atherosclerosis

1. Superficial erosion of intima endothelial monolayer

2. Disruption of atherosclerotic microvessels

3. Disruption of fibrous cap integrity

Inflammatory Modulators

Monocyte adhesion

Vascular Cell Adhesion Molecule-1 (VCAM-1)

Cytokines

Interleukin-6 (IL-6)

Tumor Necrosis Factor- γ (TNF- γ)

Modified Lipoproteins and reactive species

Oxidized phospholipids (OxPLs, O2-)

Short-chain aldehydes

Acute phase reactants

High-sensitivity C-reactive protein (hsCRP)

Fibrinogen

High sensitivity C-reactive proteinCLINICAL UTILITY, PREDICTIVE ABILITY

Flow




Background




High sensitivity C-reactive protein (hsCRP)

Protein produced in response to trauma or infection

Binds phosphocholine residues expressed on:

Microbial surfaces

Modified (or native) plasma lipoproteins

Damaged cell membranes & apoptotic cells

Assists in compliment binding and phagocytosis

CRP cycle2

CRP3

Induces complement

activation

Induces production of cell adhesion

molecules

Attenuates nitric oxide production

Mediates LDL uptake by

macrophages

Blunting of endothelial

vasoreactivity

Induces production of

tissue factor in monocytes

Facilitates monocyte

recruitment into arterial wall

Triggers oxidation of

LDL cholesterol

Endothelial dysfunction (OxLDL-CRP)22

Atherogenic LDL–induced endothelial dysfunction

hsCRP is able to specifically bind OxLDL but not nonoxidized, native LDL

hsCRP has been shown to enhance the binding of OxLDL to monocytic/macrophage-like cells

Don’t shoot the messenger4

Allele’s associated with increased CRP

concentrations were not associated with increased

risk for coronary heart disease

*Corrected for regression dilution in C reactive protein and potential confounding factors

CRP-CHD relationship is correlative

Clinical utility5

Emerging Risk Factors Collaboration (2012)

Meta-analysis to assess prognostic contribution of hsCRP N=167,000 primary prevention patients with

hsCRP data from over 50 prospective control trials

Addition of hsCRP into risk prediction model

hsCRP modestly increased model’s predictive ability (C-index +0.0039 )

Reclassify 5.2% of intermediate risk as high risk

Number Needed to Screen: 440* *to prevent 1 CV episode over 10-year period

HsCRP: Clinical utility per subgroupEmerging Risk Factors Collaboration (2012)

Appropriate and Inappropriate Reclassification Using Current Treatment Thresholds5,20

Relative Risk for First MI6(among apparently healthy men)

CRP < 0.72 mg/dLCRP 0.72-1.69 mg/dL

CRP >1.69 mg/dL

0

2

4

6

TC < 190 mg/dL TC 191-223mg/dL

TC >223 mg/dL

Total cholesterol

11.4

2.31.2 1.5

4.31

2.3

5.3Relative risk for CHD

Ridker PM et al. N Engl J Med 2002;347:1557-1565.

Relative Risk for CVD19(among apparently healthy women)

HsCRP: estimating risk7

Strong evidence hsCRP associated with CHD events

RR (95% CI): 1.58 (1.37-1.83) for incidence of CHD in persons with hsCRP >3.0mg/L compared to <1.0mg/L (adjusted for traditional Framingham risk variables)

Moderate, consistent evidence of clinical utility in risk prediction among intermediate risk patients, though few studies have looked at the reclassification in those patients

Meta-analysis and systematic review for the US Prevention Services Task Force

Past guideline recommendations

Primary prevention:

Persons with moderately high CVD risk (Framingham Risk Score 10-20% ) may benefit from statin with > 2 additional risk factors:

o Risk factor: hsCRP>3.0mg/L, TG > 200 mg/dL, non-HDL > 160 mg/dL, (+) FH premature ASCVD, (+) smoking, metabolic syndrome, CAC > 75th percentile,

Primary Prevention:

In those with intermediate risk (10-20% 10-yr CHD risk) hsCRP may help direct further evaluation and therapy “at the discretion of the physician”

Secondary Prevention:

Patients with stable coronary disease or ACS, hsCRP useful as an independent marker of risk of recurrent events, including death, MI, and restenosis after PCI

NCEP ATP-III guidelines (2004)8 CDC/AHA (2003)9

CDC/AHA continued

Measurements should be done twice (separated by > 2-wks)

May be fasting or non-fasting

Evaluate for other sources of inflammation/infection if > 10mg/L

Risk Level hsCRP (mg/L)Low Risk < 1.0 mg/LIntermediate Risk 1.0-3.0 mg/LHigh Risk >3.0mg/L

Thresholds have changed

Current guidelines

If decision is unclear, additional risk factors may be used to inform treatment decision

Primary prevention patients with unclear indication:

1. 10-yr ASCVD risk < 5%

2. DM + age < 40 or >75 years

3. LDL < 70 mg/dL

4. Age <40 or >75 years + LDL < 190 mg/dL

Critical Question 1: Risk reclassification using hsCRP in addition to the variables considered in traditional risk scores?

Risk Factor: hsCRP >2.0mg/L

supports upward risk revision, but ould not be evaluated for utility in ASCVD risk calculation model

AHA/ACC Cholesterol Guidelines (2013)10

COR: IIb, LOE: B

Other guideline recommendations

Although there is an association between elevated CRP levels and coronary heart disease events, there is insufficient evidencethat a reduction in CRP levels results in fewer CVD events

The effects of using CRP in addition to traditional CVD risk factors to guide the prescription of statins for reducing CVD risk are uncertain

See separate recommendations for CVD risk assessment with non-traditional risk factors20

US Preventive Services Task Force (2016)11

Step 3—Consider quantitative risk scoring and other factors for risk refinement, particularly in patients with moderate risk:

Additional risk indicators: hsCRP >2.0 mg/L

The greatest potential utility exists for assessment of “additional risk indicators” among patients with 2 major ASCVD risk factor

National Lipid Association (2015)12 AACE/ACE (2017)13

Considered major, nontraditional ASCVD risk factor

R30. Use hsCRP to stratify ASCVD risk in individuals with a standard risk assessment that is borderline, or in those with an intermediate or higher risk with an LDL-C concentration <130 mg/dL

Strength E, Quality Moderate Grade B, BEL 2Insufficient evidence

CVD risk assessment with non-traditional risk factors (USPSTF)20

Based on evidence from the JUPITER trial

Flow



• REVERSAL


• PROVE IT

• Meta-analysis






Statins & hsCRPOUTCOMES, RCTS, META-ANALYSIS

REVERSAL14

Compare:

Pravastatin 40mg (moderate)

Atorvastatin 80mg (high)

Objective:

Effects on coronary artery atheroma burden and progression and to determine optimal lipid reduction targets in patients with established CAD (luminal narrowing between 20-50%)

LDL between 125-210mg/dL

Outcome: Percent change in total atheroma volume

(TAV) after treatment period of 1.5-yrs Directly measured coronary plaque using

volumetric intravascular ultrasound

30mm segment

REVERSAL - Design

657 patients randomizedwith evidence of coronary artery narrowing

Atorvastatin 80 mg daily (n=328)

Pravastatin 40 mg daily(n=329)

Standard of care

Duration: mean 1.5 year follow up

REVERSAL - Results

Results:

Baseline Characteristics (% or Mean):

Age: 56 years; Caucasian: 88%; Male 72%: Female 18%

Smoker: 27%, Hypertension: 69%, Diabetes: 19%, Metabolic syndrome: 40%

Baseline biomarkers:

moderate-intensity arm LDL: 150 mg/dL, hsCRP: 3.0mg/L

high-intensity arm LDL: 150.2 mg/dL, hsCRP: 2.8 mg/L

REVERSAL - Results

Biomarker Prava 40 Atorva 40 p-value*

hsCRP 3.0 2.9 mg/L (-5.2%) 2.8 1.8 mg/L (-36.4%) p<0.001

LDL 150.2 110 mg/dL (-25%) 150.2 78.9 mg/dL (-46%) p<0.001

*ANOVA used to analyze LDL and log-transformed hsCRP

REVERSAL - Results

Primary Endpoint

Total atheroma volume (TAV)mm3:

Pravastatin 40mg (moderate-intensity)

TAV median + 4.4mm3 (2.7% increase from baseline), p=0.001

Atorvastatin 40mg (high-intensity)

TAV median - 0.9mm3 (0.4% decrease from baseline), p=0.96

REVERSAL21 - Results

Relationship between the changes in hsCRP and rate of progression of atherosclerosis

Rs=0.11 (p=0.01) Rs=0.11 (p=0.02)

REVERSAL - Conclusion

Atorvastatin was significantly better than pravastatin for

Significant linear relationship noted for LDL reduction to atheroma progression

Little difference in safety/tolerability

JUPITER15

Compare:

Rosuvastatin 20mg (high intensity)

Placebo

Hypothesis: Persons with no history of cardiovascular disease nor dyslipidemia, but an elevated hsCRP (>2) may benefit from a statin

Outcome: MACE

JUPITER - Design

17,802 patients randomized

Men > 50, Women > 60, LDL < 130, hsCRP > 2

Rosuvastatin 20 mg daily

(n=8901)

Placebo

(n=8901)

Primary prevention ASA allowed

Duration: mean 1.9 year follow upPertinent exclusion: diabetes, uncontrolled hypertension, TG > 500, significant renal / hepatic dysfunction

JUPITER - Results

Age: 66, Gender: 38.2% Female: 61.8% Male

Race/ethnicity: Black or Hispanic 16.6%

Use of aspirin: 16.6%, antihypertensives (NR)

Metabolic Syndrome 41.4%, current smoker 16%, hypertension 57%

LDL:108mg/dL, HDL: 49mg/dL, TG:118mg/dL, A1c: 5.7%, hsCRP: 4.2 mg/L

CrCl: 73mL/min/1.73m2

Baseline Characteristics (% or median value)

JUPITER - Results

Biomarker Rosuva 20 Placebo p-value*

hsCRP 4.2 2.2 mg/L (-48%) 4.3 3.5 mg/L (-23%) p<0.001

LDL 108 55 mg/dL (-49%) 108 110 mg/dL (+2%) p<0.001* p-values representative of between group differences at 12 month mark p<0.001 maintained for between group comparisons from 12-48 month follow-up periods

JUPITER - Results

Primary/Secondary Endpoints(Rate/100-person years for statin vs. placebo, Hazard Ratio (HR), p-value)

MACE: Rate 0.77 vs. 1.36, HR= 0.56 (0.46-0.69), p<0.00001

Any myocardial infarction: Rate 0.17 vs. 0.37, HR=0.35, p=0.0002

Nonfatal MI similar rates/HR, significant difference

Any stroke: Rate 0.18 vs. 0.34, HR=0.52, p=0.002

Nonfatal stroke similar rates/HR, significant difference

Arterial revascularization: Rate 0.38 vs. 0.71, HR=0.54, p<0.00001

Hospitalization for unstable angina Rate 0.09 vs. 0.14, HR=0.59, NS

All-cause mortality: Rate 1.0 vs. 1.25, HR=0.80, p=0.02

NNTs 95 (2-yr time frame) 31 (4-yr time frame)

Estimated with treatment for 5 years

NNT: 25

JUPITER – Results (safety)

No significant difference in number of serious adverse events

Myopathy not significantly different

Diabetes

Physician-reported diabetes significantly higher with statin

270 statin vs. 216 placebo, p=0.01

A1c at 24-months significantly higher with statin

5.9% statin vs. 5.8% placebo, p=0.001

Transaminitis, GI/hepatic/hematologic disorders, cancer, intracranial hemorrhage not significantly different

JUPITER- Conclusions

Patients without cardiovascular disease and LDL < 130mg/dL, but hsCRP > 2mg/L randomized to receive rosuvastatin 20mg/d experienced:

44% relative risk reduction in MACE

20% relative risk reduction in all-cause mortality

Results similar in low risk populations (e.g. Framingham <10% 10-yr risk & no major ASCVD risk factors)

Similar incidence of adverse effects compared to placebo

Monitoring was far more intensive than typical practice or guideline standards

HOPE-316

Similar to JUPITER – no established CVD, intermediate risk

Was more inclusive of different races and ethnic groups (40% Asian, 27% Hispanic, 1.8% black) in low- & middle-income countries and lasted longer (median 5.6 years)

Comparing:

Rosuvastatin 10mg (moderate)

Placebo

Co-Primary Outcome 1: MACE

Co-primary Outcome 2: MACE + revascularization, cardiac arrest, HF

HOPE-3 - Design

12,705 patients randomized

Men > 55 & Women > 65 + > 1 CV risk factor (“intermediate”)

Rosuvastatin 10 mg daily

(n=6361)

Placebo

(n=6344)

Primary prevention ASA

Duration: median 5.6 year follow up*There were actually 4 arms to accommodate HCTZ/candesartan +/- rosuvastatin +/- placebo

HOPE-3 - Results

Figure S14: Selected Subgroup Analysis for Co-Primary Outcome 1: MACE

Figure S15: Selected Subgroup Analysis for Co-Primary Outcome 2: MACE++

PROVE IT-TIMI 2217

A pre-specified subgroup analysis18

Comparison:

Atorvastatin 80 mg (high intensity)

Pravastatin 40mg (moderate intensity)

Hypothesis: Patients with acute coronary syndromes (ACS) would have a lower recurrence of MI or death from coronary causes by reducing hsCRP levels as a result of statin therapy, independent of LDL cholesterol levels

Biomarker goals: Achieve an LDL <70mg/dL and hsCRP <2.0mg/L

Primary Outcome: MACE

PROVE IT - Design

4162 patients randomized with an ACS < 10 days (stable)

Atorvastatin 80 mg daily (n=2099)

Pravastatin 40 mg daily (n=2063)

ASA + standard medical therapy

Duration: mean 2 year follow up*Event-driven duration, ongoing until >925 events

For the hsCRP subgroup, a total of N=3,745 randomized

PROVE IT- Results

Baseline Characteristics (% or median (IQR)):

22% female: 78% male; 90% Caucasian

36% hypertension, 17% diabetes, 36% current smokers

25% had previously used a statin

19% with previous MI, 15% with previous PCI, 11% with previous CABG


PRAVA 40 arm LDL: 106 mg/dL (87-127); hsCRP: 12.3mg/L

ATORVA 80 arm LDL: 106 mg/dL (89-128); hsCRP: 12.3mg/L

PROVE IT - Results

Primary Endpoint:

Met LDL goal < 70mg/dL

Age-adjusted event rate 2.7 versus 4.0 per 100 person-years, p=0.008

Met hsCRP goal <2.0mg/L

Age-adjusted event rate 2.8 versus 3.9 per 100 person-years, p=0.006

Recurrent MI or CV death

Ridker PM et al. N Engl J Med 2005;352:20-28.

Only 3% of the variation in “achieved CRP levels” was explained by the variation in “achieved LDL cholesterol levels”

PROVE IT- Results

Relationship between LDL cholesterol and hsCRP levels

(r=0.16, P=0.001)

PROVE IT- Results

Groups stratified by biomarker N Age-Adjusted,

event rate P-value

1 LDL > 70mg/dLhsCRP > 2.0 mg/L

1086 4.6 per 100 person-years

P<0.001

2 LDL > 70mg/dLhsCRP < 2.0 mg/L


3 LDL < 70mg/dLhsCRP > 2.0 mg/L


4 LDL < 70mg/dLhsCRP < 2.0 mg/L


LDL < 70 mg/dLLDL > 70 mg/dL

hsCRP < 2mg/L

hsCRP > 2mg/L

2.43.1

3.2

4.6

Event Rates(per 100 person-years)

PROVE IT-TIMI 22 cont.

A post hoc assessment of hsCRP threshold of 1.0mg/L showed age-adjusted event rates of:

Groups stratified by biomarker Age-Adjusted, event rate P-value1 LDL > 70mg/dL; hsCRP > 1.0 mg/L 4.5 per 100 person-years

P<0.0012 LDL > 70mg/dL; hsCRP < 1.0 mg/L 2.3 per 100 person-years3 LDL < 70mg/dL; hsCRP > 1.0 mg/L 3.1 per 100 person-years4 LDL < 70mg/dL; hsCRP < 1.0 mg/L 1.9 per 100 person-years

PROVE IT- Conclusion

Persons who achieved both a reduction in LDL <70mg/dL and hsCRP <2.0mg/L had significantly lower rates of recurrent MI & CV Death (regardless of the statin used)

Achieving only LDL < 70 mg/dL had similar event rate to only hsCRP < 2.0 mg/L

An independent linear relationship existed for achieved levels of LDL (<70) and hsCRP (<2) on risk of recurrent MI or CV death, despite adjustments for concomitant cardiovascular medications

NNT (to LDL < 70 and hsCRP < 2) = 1/(0.0449580378-0.02371429024) = 47*to prevent 1 event, as compared to LDL > 70 and hsCRP > 2

Meta-analysis23

Inclusion of > 50 prospective studies with individual participant data (n=160,309)

RCTs, cohort, case-control studies included

Persons had no history of vascular disease (primary prevention)

For every 1-SD (i.e. 1.11 loge CRP) increase in CRP adjusted for age & sex:

Risk Ratio all vascular death: 1.82 (1.66-2.0), p<0.0001

Risk Ratio all non-vascular deaths: 1.55 (1.46-1.66), p<0.0001

Meta-analysis - Results

All Vascular Deaths

All Non-Vascular DeathsRisk Ratio

Risk Ratio

Fewer adjustments

Greater adjustments


Risk Ratio

Risk Ratio

Coronary Heart Disease

Ischemic Stroke

Fewer adjustments

Greater adjustments


Direct comparison of risk ratios for CHD per 1-SD higher loge [CRP] with those of systolic blood pressure and lipids, mutually adjusted for each other plus other conventional risk factors

Flow



• REVERSAL


• PROVE IT

• Meta-analysis



Canakinumab




• Interleukin-1β

• CANTOS trial


CanakinumabINTERLEUKIN-1 BETA INHIBITOR

Interleukin-1β and Canakinumab24

Canakinumab (ILARIS®) is already approved for use in a variety of autoimmune disorders

Inhibits the inflammatory biomarker IL-1 β, whish is associated with increased hsCRP concentrations and cardiovascular events

IL-1 β is produced by vascular cell walls (and elsewhere) and works mostly extracellularly as a soluble mediator

Caspase-1, responsible for the activation of IL-1β, is expressed by foam cells within atherosclerotic plaques

MMP = matrix metalloproteinase

Interleukin-1β and Canakinumab24

CANTOS25

Comparison:

Placebo

Canakinumab 50mg subcutaneously every 3 months (after first 2 doses)



Question: Will inhibition of IL-1β and subsequent inflammation without any lowering of LDL have a significant effect on CV outcomes in persons with ACS compared to placebo?

Primary outcome: MACE

Secondary outcome: primary + hospitalization for UA revascularization

CANTOS - Design

10,061 patients randomized with history of MI and CRP > 2

Canakinumab50 mg q3mo

(n=2170)

Placebo

(n=3344)

Standard medical care (e.g. ASA, statins, BP meds)

Duration: median 3.7 year follow up


(n=2284)


(n=2263)

CANTOS - Results

Results:

Baseline Characteristics (% or Mean):

Age: 61 years; Race: NR; Male 75%, Female 25%

BMI: 30 kg/m2

Use of RAAS-inhibitor: 80%; statin: 92%; or ASA: 95%

Smoker: 23%; Hypertension: 80%; Diabetes: 40%


LDL: 81 mg/dL; hsCRP: 4.15mg/L; IL-6: 2.5 ng/L

CANTOS - Results

-18.8%

Change in hsCRP levels over 48 months

-41.7%

-53.9%-58.8%

Change in lipids over 48 months

CANTOS- Results

Primary Outcome:

15% lower risk for MACE with canakinumab 150mg versus placebo (p=0.021)

Secondary Outcome:

17% lower risk for MACE with canakinumab 150mg versus placebo (p=0.005)

Any serious adverse event:

no significant difference between canakinumab at any dose compared to placebo

CANTOS - Results

Only the 150mg dose met the pre-specified, multiplicity-adjusted threshold for statistical significance

Canakinumab 150mg v. placebo

Canakinumab 300mg v. placeboCanakinumab 50mg v. placebo

P-value<0.02115

CANTOS- Results

0.06

0.24

0.43

0.18

0.1

0.4

0.6

0.31

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7

Neutropenia

Leukopenia

Thrombocytopenia

Fatal infection or sepsis

Incidence rate (per 100 person-years)

Adverse EventsCombined canakinumab Placebo

CANTOS- Results

0.64

3.32

0.8

0.45

2.26

0.38

0 0.5 1 1.5 2 2.5 3 3.5

Fatal cancer

Any arthritis

Gout

Incidence rate (per 100 person-years)

Other Relevant Events Combined canakinumab Placebo

CANTOS- Conclusion

Persons with a history of ACS receiving standard of care therapies (e.g.

statins, ASA, RAAS inhibitor) had a 15% reduction in MACE with canakinumab 150mg vs. placebo

Serious adverse events were similar, but there are notable severe adverse events (blood dyscracias and infection) that were higher with canakinumab (fatal infection/sepsis NNH = 777)

NNT with canakinumab 150mg x48 mo = 163*versus placebo

Flow



• REVERSAL


• PROVE IT

• Meta-analysis



Canakinumab Conclusions




• Interleukin-1β

• CANTOS trial


• Use of hsCRP to guide treatment decision-making and ASCVD lowering therapy

ConclusionsPRACTICAL APPLICATION

LDL and hsCRP

Both are strong predictors of cardiovascular disease, but are interpreted differently

LDL hsCRP LDL measurements in the blood give us

inference about lipid burden on vasculature

Does not directly reflect damage already done to vasculature or active inflammatory process

Statins reduce LDL, resulting in a lower event rate

hsCRP measurements give us an inference about inflammation throughout the body, including plaque and vasculature

Relatively non-specific, but sensitive for inflammation in atherosclerotic disease

Statins and novel anti-inflammatory therapies (canakinumab) reduce hsCRP, resulting in a lower event rate

Who will benefit the most?

HsCRP can help re-classify risk in persons where risk (and use of risk reducing therapies) is unclear

There are many clinical scenarios where risk may be unclear, but some gray areas to consider:

AGE < 40 or > 75 (and LDL < 190)

ASCVD risk < 7.5% (no DM and age 40-75)

LDL < 70 mg/dL (but other major ASCVD risk factors or clinical ASCVD)

Receiving a statin, but a higher intensity may be indicated

HsCRP pearls

Lab cost is roughly $20 (varies)

Most widely recognized threshold for elevated hsCRP = 2.0 mg/L

Most data exist for use in primary care, though it is not uncommon to see hsCRP trends during ACS (different values are expected)

Samples should be re-checked (x1) if elevated/abnormal

Values > 10 mg/L should prompt investigation into other possible causes (e.g. other inflammatory conditions & infection)

3 months is sufficient to see hsCRP levels reach nadir & plateau after initiating an intervention

Flow diagram with thresholds

JUPITER PROVE-IT (substudy)

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An anti-inflammatory approach to ASCVD prevention

DR. SCOTT A. COON, PHARMD, BCPS, BCACP

[email protected]

OCTOBER 2018

Documents

An anti-inflammatory approach to ASCVD prevention · HsCRP: estimating risk7 Strong evidence hsCRP associated with CHD events RR (95% CI): 1.58 (1.37-1.83) for incidence of CHD in