The grey zone: What to do for the “intermediate risk” patient?

Lifestyle-Heart Hypothesis

Mozaffarian et al. Circulation 2008;117;3031-3038

Atherosclerosis: Traditional and novel risk factors

Interheart: Developed and developing countries (N = approx 30,000)

IHD Risk Factor Odds Ratio Population

attributable risk ApoB/ApoAI 3.25 49% Smoking 2.87 36% Hypertension 1.91 18% Diabetes 2.37 10% Abdominal obesity 1.12 – 1.62 20% Psychosocial 2.67 33% Diet (fruit & veg) 0.70 14% Activity 0.86 12% Alcohol (not binge) 0.91 7%

Atheroma: Stages and timeframe

Atheroma is proportional to the number and severity of classic risk factors

Where is mypatient?

Novel risk factors and atheroma

Development of an atheroma

ß-VLDL = beta-very low-density lipoprotein; Lp(a) = lipoprotein (a); VCAM-1 = vascular cell adhesion molecule-1; ICAM-1 = intercellular adhesion molecule-1; MCP-1 = monocyte chemoattractant protein-1; CCR-2 = specific receptor present on the surface of monocytes; oxLDL = oxidized low-density lipoprotein; MMP = matrix metalloproteinases; GM-CSF = granulocyte macrophage-colony stimulating factor; SR-A = macrophage scavenger receptor class A

Monocyte

Induction of adhesionmolecules and chemotaxis

AdhesionVCAM-1ICAM-1P-selectinE-selectin

MigrationMCP-1CCR-2oxLDL

oxidation

CytokinesMMPsEndothelin-1

Endothelialcells

Smooth muscle cells

Inti

ma

Internal elastic lamina

Lum

en

CD36SR-A

Differentiation(GM-CSF)

MacrophageFoam cell

T lymphocyte

CD40

IFN-gamma

LDL-C, β-VLDL, Lp(a)

Adapted with permission from Fan et al, J Atheroscler Thromb 2003; 10: 63

Integration of risk factors: Risk calculators

Limitations of CVD Risk Assessment

• Underlying data (eg FRS) is historical, geographical• Suitable for non-western populations in 21st century?

• Some data components are infrequently available• Left ventricular hypertrophy

• No mechanism to take advantage of risk predictors• High sensitivity C-reactive protein etc

• Predominant effect of age • Assigns low 10-year risk to some patients with moderate to

high lifetime risk who might benefit from more aggressive management, particularly in women & younger men

• Omits or fails to quantify several major risk factors• Family history, smoking, diabetes.

High sensitivity C-reactive protein as a discriminator in intermediate risk?

US Preventive Services Task Force (2009) “CRP is associated with CHD events....Adding CRP to risk prediction models among initially intermediate risk persons improved risk stratification. However.. evidence that reducing CRP levels prevents CHD is lacking” “ the current evidence is insufficient to assess the balance of benefits and harms of using the non-traditional risk factors studied to screen asymptomatic men and women with no history of CHD to prevent CHD events.”

American Heart Assoc and CDC (2008) “the entire adult population should not be screened for hs-CRP for the purposes of CVD risk assessment.”

Additional analytes, improved assays or evidence of benefits of combinations of assays may in future be found to have advantages, but further research is needed”

Canadian Cardiovascular Society (2009) “men older than 50 years and women older than 60 years of age, of intermediate risk whose LDL-C does not already suggest treatment, hs-CRP can be used for risk stratification”

Clinical risks: Microalbuminuria, renal impairment and inflammatory disorders

Markers of end-organ damage

BNPHs-TnT

Genetic evidence for additional risks factors

Non-invasive imaging detects sub-clinical atheroma

Shaw et al. Radiology 2003; 228:826-833 Raggi P et al. Arterioscler Thromb Vasc Biol. 2004;24:1272-77

Primary Author

Study TypeNo of Patients

Mean Follow-up (years)

Type of EventsNo of events

Incremental Prognostic Value of Coronary Calcium

Shaw L 2 Observational 10,377 5 All-cause death 249 Yes

Kondos G 1Observational

5,635 3Myocardial Infarction,

Death and Revascularizations

224 Not Assessed

Greenland P 5

Prospective1,029 7.0 (median)

Myocardial Infarction and Death

84 Yes

LaMonte M 6Prospective

10,746 3.5

Myocardial Infarction and Cardiovascular

Death 81 Yes

Arad Y 4 Prospective 4,613 4.3Atherosclerotic

Cardiovascular Events119 Yes

Taylor A 7 Prospective 1,983 3Acute Coronary

Syndrome and Sudden Cardiac Death

9 Yes

Detrano R 8 Prospective 6,722 3.8Myocardial Infarction and Cardiovascular

Death89 Yes

Becker A 9 Prospective 1,726 3.4Myocardial Infarction and Cardiovascular

Death179 Yes

Reclassification of intermediate risk patients

Where to set the risk threshold? Benefit versus risk or benefit versus cost?

“If statins cost $4/month, treatment thresholds of low-density lipoprotein cholesterol > 4 mmol/l for low-risk persons (0 to 1 risk factor), >3.3 mmol/l for moderate-risk persons (≥2 risk factors and 10-year risk <10%), and >2.6 mg/dL for moderately high-risk persons (≥2 risk factors and 10-year risk >10%) would reduce annual healthcare costs by $430 million compared with Adult Treatment Panel III guidelines”. Lazar LD. Circ 124:146-53

Strategies that compete with the absolute risk approach.

Epidemiological methods identify risk factors

The more independent risk factors for aoutcome / disease, the worse each islikely to perform on its own as a

predictor What matters is the amount of the total risk

attributable to the risk factor

Establishing a risk factor


Lowest fifth Highest fifth


Rate of disease = 5 / 1000

Rate of disease = 50 / 1000

Incidence ratio = (50/1000) / (5/1000) = 10

Odds ratio = (50/950) / (5/995) 10

60% of thepopulation!


1. Law MR, Watt HC, Wald NJ,.

Threshold risk factor

Threshold

Continuous risk factor

No threshold

O.R.

What happens when you treat?

Cholesterol

x

x?

Summary and transition to cases

• deCODE MI re class, 2 cases• Complex cases 1

Cholesterol reduction

Reduction in risk in treatment group

Trial Net change in TC

Incidence of major coronary

events in placebo group

(%/yr)

Relative (%) Absolute (%/yr)

WOSCOPS 1.7 mmol/L 1.4 39 (20 – 52) 0.5 (0.3 –

0.7)*

4S 1.4 mmol/L 5.2 35 (27 – 42) 1.8 (1.4 –

2.2)*

1. Shepherd J, Cobbe S, et al., Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. New England Journal of Medicine, 1995. 333(20):1301.






(%/yr)


WOSCOPS 1.7 mmol/L 1.4 39 (20 – 52) 0.5 (0.3 –

0.7)*

4S 1.4 mmol/L 5.2 35 (27 – 42) 1.8 (1.4 –

2.2)*

1. Scandinavian Simvastatin Survival Study Group, Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994. 344(8934):1383.






(%/yr)


WOSCOPS 1.7 mmol/L 1.4 39 (20 – 52) 0.5 (0.3 –

0.7)*

4S 1.4 mmol/L 5.2 35 (27 – 42) 1.8 (1.4 –

2.2)*

Systolic blood pressure

Usual SBP (mmHg)

Floa

ting

Abs

olut

e R

isk

& 9

5% C

I

110 120 130 140 150 160 170

0.25

0.50

1.00

2.00

4.00

8.00

1. Asia-Pacific Cohort Studies Collaboration, Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet, 1994. 344(8934):1383.

Odd

s ra

tio f

or C

HD

Coronary disease

Odd

s ra

tio f

or C

HD

Coronary disease

O.R.

Usual diastolic blood pressure (mmHg)

Diastolic blood pressure

Stroke

MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke and coronary heart disease. 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias . Lancet 1990;335:765 74.

Diastolic blood pressureO

dds

ratio

for

CH

D

Coronary disease

O.R.

Usual diastolic blood pressure (mmHg)

Stroke

MacMahon S, Peto R, Cutler J, Collins R, Sorlie P, Neaton J, et al. Blood pressure, stroke and coronary heart disease. 1. Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias . Lancet 1990;335:765 74.

Smoking

Yusuf S, Hawken S, et al. 2004: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 364(9438): p. 937.

Yusuf S, Hawken S, et al. 2004: Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet, 364(9438): p. 937.

Attributable risk

1. Law MR, Watt HC, Wald NJ,.

Framingham equation

= 0 + 1 x female + 2 x log(age) + 3 x log(age) x female + 4 x [log(age)]2 x female + 5 x log(SBP) + 6 x cigarettes + 7 x log(TC/HDL) + 8 x diabetes + 9 x diabetes x female + 10 LVH

= exp(0 + 1 )

u = [log(10)] - ] /

10 y predicted P for CHD = 1 – exp(-exp(u))

Framingham equation mismatches

Framingham equation recalibration

Limitations

Underestimates for extremes of risk factors Younger people have lower risk

– But more life years lost• Consider projecting risk forward in time• Normalising for age

New/novel risk factors• Continuous HbA1c• hsCRP• Lp(a)• Apo E4/E4• Obesity• CKD

Implications of global risk approach

Treat anyone at high risk

1. Law MR, Watt HC, Wald NJ, The Underlying Risk of Death After Myocardial Infarction in the Absence of Treatment . Archives of Internal Medicine, 2002;162(21):2405.

The major determinant of risk is existing disease

Untreated MI: – Death rates for first event: 36%

• Before hospital 23%• During admission 16% (of those admitted)

– Subsequent events: 53%• Before hospital 33%• During admission 30%




Untreated MI: First event– Death rates for first year: 10.3%

• Stroke & heart disease 9.6%

– Annual death rate 5.3% (for life)• Stroke & heart disease 4.6%

Subsequent events:• First year 21% (19% CVD)• Annual death rate 12% (10% CVD)



Implications of global risk approach

Not just the “abnormal” ones

Change all the risk factors together

25%

25% >50%



1. Australian Institute of Health and Welfare. Heart, stroke and vascular diseases: Australian Facts 2004. AIHW.

fixrhubarbzumab

fixrhubarbzumab

Don’t do unnecessary trials

?


Adapted from:Law MR, Wald NJ, Risk factor thresholds: their existence under scrutiny. BMJ, 2002;324:1570.


Cost efficacy

Mr J.S.• Mr J.S. has a history consistent with Familial Combined Hyperlipidaemia. He

is 49 years old, BP 150/90 and his lipids include: TC = 7.8 mmol/l, TG = 2.7 mmol/l, HDL = 1.1 mmol/l, LDL = 5.6 mmol/l. His older brother, who, like J.S, was a non smoker, suffered onset of CVD at this age. J.S.’s total CVD risk is 14%

Questions concerning Mr J.S.

• Does he warrant lipid-lowering treatment according to NHF guidelines? Yes / No

• A colleague suggests that his ankle:brachial index should be measured. Is this non invasive test for CVD risk A) Specific B) Sensitive C) Both

• Could his risk assessment be improved by Genome Wide Association Studies? Yes / No

• Mr J.S. has a history consistent with Familial Combined Hyperlipidaemia. He is 49 years old, BP 150/90 and his lipids include: TC = 7.8 mmol/l, TG = 2.7 mmol/l, HDL = 1.1 mmol/l, LDL = 5.6 mmol/l. His older brother, who, like J.S, was a non smoker, suffered onset of CVD at this age. J.S.’s total CVD risk is 14%

• Does he warrant lipid-lowering treatment according to NHF guidelines? Yes / No

• A colleague suggests that his ankle:brachial index should be measured. Is this non invasive test for CVD risk A) Specific B) Sensitive C) Both

• Could his risk assessment be improved by Genome Wide Association Studies? Yes / No

Does he warrant lipid-lowering treatment according to NHF guidelines?

• Yes

• No

Does he warrant lipid-lowering treatment according to NHF guidelines?

The case for “Yes”

Others with elevated absolute risk of CVDLipid-modifying therapy is indicated for those with: C◦ absolute risk ≥15% of a CVD event in the next 5 years or◦ absolute risk 10–15% of a CVD event in the next 5 years when either of the following is present:- family history of premature CHD (first degree relative who developed CHD before age 60)- the metabolic syndrome

2005 Update of NHF Lipid Management Guidelines

A colleague suggests that his ankle:brachial index should be measured. Is this non-

invasive test for CVD risk...

• : A) Specific

• B) Sensitive

• C) Both

A colleague suggests that his ankle:brachial index should be measured. Is this non-

invasive test for CVD risk...The case for “A”

Arteriosclerosis, Thrombosis, and Vascular Biology.2005; 25: 1463-146

Sensitivity and Specificity of the Ankle–Brachial Index to Predict Future Cardiovascular Outcomes A Systematic Review Anand V. Doobay, Sonia S. Anand

The sensitivity and specificity of a low ankle–brachial index to predict incident coronary heart diseases were 16.5% and 92.7%, for incident stroke were 16.0% and 92.2%, and for cardiovascular mortality were 41.0% and 87.9%, respectively. The corresponding positive likelihood ratios were 2.53 (95% CI, 1.45 to 4.40) for coronary heart disease, 2.45 (95% CI, 1.76 to 3.41) for stroke, and 5.61 (95% CI, 3.45 to 9.13) for cardiovascular death.

http://atvb.ahajournals.org/search?author1=Anand+V.+Doobay&sortspec=date&submit=Submit



http://atvb.ahajournals.org/search?author1=Sonia+S.+Anand&sortspec=date&submit=Submit

http://atvb.ahajournals.org/search?author1=Sonia+S.+Anand&sortspec=date&submit=Submit

Could his risk assessment be improved by Genome Wide Association Studies?

• Yes

• No

Could his risk assessment be improved by Genome Wide Association Studies?

The case for “No”?

C N (%)

GN (%)

2 (1df)

P-value

Cases 2,132 (55.4) 1,716 (44.6)55.1 1.2 x 10-13

Controls 2,783 (47.4) 3,089 (52.6)

Allelic Odds Ratio = 1.38

CC N (%)

CG N (%)

GGN (%)

2

(2df) P-value

Cases 586 (30.5) 960 (49.9) 378 (19.6)59.7 1.1 x 10-14

Controls 676 (23.0) 1,431 (48.7) 829 (28.2)

Heterozygote Odds Ratio = 1.47

Homozygote Odds Ratio = 1.90

Samani N et al, N Engl J Med 2007; 357:443-453.

Number of Variants

Measured

European ancestry 16

East Asian ancestry 3

The deCODEme Complete Scan identifies validated MI risk variants and uses them to provide a personalized interpretation of the associated genetic risk for having a heart attack. The number of variants included in the deCODEme Complete Scan for each ethnic group are listed in the table below.

Mr J.S (continued).• Mr J.S does not have chest pain or any exertional symptoms, but he had an

anaphylactic reaction, which may have been related to the introduction of statins.

• He remained off statin, but then developed atypical chest pain.

More questions regarding Mr J.S.• Which non-invasive test would you favour to weigh up risks versus benefits

of re-attempting statin therapy? A) CT coronary angiogram B) Sestamibi perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

• Which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? (more than 1 possible)

A) CT coronary angiogram B) Sestamibi perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

He underwent CT coronary angiogram which suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?

Underestimate / Overestimate / Neither

• Mr J.S does not have chest pain or any exertional symptoms, but he had an anaphylactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh up risks versus benefits of re-attempting statin therapy? A) CT coronary angiogram B) Sestamibi perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

• If he remained off statin, which of the previous tests would you be prepared to repeat on a 2 to 3 yearly basis? (more than 1 possible)

A) CT coronary angiogram B) Sestamibi perfusion scan C) Stress Echo D) Coronary Calcium Score E) Exercise ECG

Mr J.S. Developed atypical chest pain and underwent CT coronary angiogram which suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to underestimate or overestimate disease severity?

Underestimate / Overestimate / Neither

Mr J.S does not have chest pain or any exertional symptoms, but he had an

anaphylactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh

up risks versus benefits of re-attempting statin therapy?

• A) CT coronary angiogram •

• B) Sestamibi perfusion scan•

• C) Stress Echo

• D) Coronary Calcium Score•

• E) Exercise ECG

Mr J.S does not have chest pain or any exertional symptoms, but he had an

anaphyllactic reaction, which may have been related to the introduction of statins. Which non-invasive test would you favour to weigh

up risks versus benefits of re-attempting statin therapy?

The case for “D”, but “C” and “E” reasonable

If he remained off statin, which of the previous tests would you be prepared to

repeat on a 2 to 3 yearly basis? (more than 1 possible)

A) CT coronary angiogram

B) Sestamibi perfusion scan

C) Stress Echo

D) Coronary Calcium Score

E) Exercise ECG

If he remained off statin, which of the previous tests would you be prepared to

repeat on a 2 to 3 yearly basis? The case for “D” (“C” and “E” reasonable)

Mr J.S. developed atypical chest pain and underwent CT coronary angiogram which

suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to

underestimate or overestimate disease severity?

Underestimate

Overestimate.

Neither

Mr J.S. developed atypical chest pain and underwent CT coronary angiogram which

suggested 70% stenosis in 2 vessels. Does CT coronary angiography tend to

underestimate or overestimate disease severity?

The case for “B”Heart 2011;97:1363-1364 CT coronary angiography: a new unique prognosticator?Lisan A Neefjes, Pim J de Feyter.CTCA tends to overestimate the severity of the coronary stenosis, resulting in a number of patients with false-positive outcomes that is too high. This is mainly caused by the blooming effect of calcified lesions in combination with the still too limited spatial resolution of CTCA as compared with invasive coronary angiography. CTCA provides, additional to luminography, comprehensive assessment of the anatomical manifestations of coronary atherosclerosis, including the distribution (proximal, mid and distal) and extent (one-, two-, three-vessel disease, left main disease) of CAD, the presence of ‘positive remodelling’ of the vessel and a, rather crude, assessment of the coronary plaque components (calcified, non-calcified and mixed)

http://heart.bmj.com/search?author1=Lisan+A+Neefjes&sortspec=date&submit=Submit



http://heart.bmj.com/search?author1=Pim+J+de+Feyter&sortspec=date&submit=Submit



Ms A.Y.• Ms A.Y is a 53 year-old woman with a 20 year history of severe rheumatoid

arthritis. She is suffering a flare-up despite systemic steroid therapy and steroid sparing agents. Central chest pain is consistent with pericarditis, but cardiovascular risk assessment is thought to be justified. BP (115/75) is normal but creatinine is mildly elevated (112 umol/l). TC = 5.7, TG = 2.6, HDL = 0.9 mmol/l, LDL = 3.6 mmol/l. Family history is unremarkable but uncertainty concerning her risk prompts measurement of hs-CRP (5 mg/l), lipoprotein (a), (678 mg/l) and total homocysteine, (23 umol/l) all of which are elevated.

Questions concerning Ms A.Y.

• Calculated 5 year risk is 2%. Do you agree with this estimation? Yes / No

• Which of the following is unlikely to be affected by the inflammatory state? A) Lipid profile B) hs-CRP C) Lipoprotein (a) D) homocysteine

• Which of the following is less likely to be affected by the renal impairment? A) Lipid profile B) hs-CRP C) Lipoprotein (a) D) homocysteine

• How much is Ms A.Y’s RELATIVE risk of CVD increased? A) 20% B) 50% C) 100% D) 200% E) More than 200%

• Ms A.Y is a 53 year-old woman with a 20 year history of severe rheumatoid arthritis. She is suffering a flare-up despite systemic steroid therapy and steroid sparing agents. Central chest pain is consistent with pericarditis, but cardiovascular risk assessment is thought to be justified. BP (115/75) is normal but creatinine is mildly elevated (112 umol/l). TC = 5.7, TG = 2.6, HDL = 0.9 mmol/l, LDL = 3.6 mmol/l. Family history is unremarkable but uncertainty concerning her risk prompts measurement of hs-CRP (5 mg/l), lipoprotein (a), (678 mg/l) and total homocysteine, (23 umol/l) all of which are elevated.

• Calculated 5 year risk is 2%. Do you agree with this estimation? Yes / No

• Which of the following is less likely to be affected by the inflammatory state? A) Lipid profile B) hs-CRP C) Lipoprotein (a) D) homocysteine

• Which of the following is unlikely to be affected by the renal impairment? A) Lipid profile B) hs-CRP C) Lipoprotein (a) D) homocysteine

• How much is Ms A.Y’s RELATIVE risk of CVD increased? A) 20% B) 50% C) 100% D) 200% E) More than 200%

Calculated 5 year risk is 2%. Do you agree with this estimation?

• Yes

• No

Calculated 5 year risk is 2%. Do you agree with this estimation?

The case for “No”

Study n OR (SMR)

ORALE1 236 3.17 (adj)

Rochester Cohort2 603 2.12 (MI)

Nurses Health Study3 527 2.0

Stockport Inception cohort4 1010 1.93

Van Doornum et al.5 - 1.70 overall mortality

Maradit-Kremers H, et al. Arthritis Rheum 2005; 52:722–732; 3. Solomon DH, et al. Circulation 2003; 107:1303–1307; 4. Goodson N, et al. Ann Rheum Dis 2005; 64:1595–601; 5. Van Doornum S, et al. Arthritis Rheum 2002; 46: 862–73

Which of the following is less likely to be affected by the inflammatory state?

• A) Lipid profile

• B) hs-CRP

• C) Lipoprotein (a)

• D) homocysteine

• E) None of the above

Which of the following is less likely to be affected by the inflammatory state?

The case for “E”

Circulating Homocysteine Is An Inflammation Marker And A Risk Factor of Life-Threatening Inflammatory Diseases J Biomed Lab Sci 2007 James T. Wu

Deficiency in vitamin B6, B12 or folate is the major cause of hyperhomocysteinemia. Since inflammation promotes cell proliferation at the expense of excess amount of vitamins, therefore, hyperhomocysteinemia may indicate the presence of inflammation. Moreover, inflammation enhances the synthesis of nitric oxide, which again produces hyperhomocysteinemia through binding with vitamin B12. Consequently, varying degrees of hyperhomocysteinemia are detectable in all inflammatory diseases

Which of the following is unlikely to be affected by the renal impairment?

• A) Lipid profile

• B) hs-CRP

• C) Lipoprotein (a)

• D) homocysteine

• E) None of the above

Which of the following is unlikely to be affected by the renal impairment?

The case for “E”

C-reactive protein, cardiovascular risk, and renal disease in a remote AustralianAboriginal community. Clinical Science 106, 121–128Stephen McDONALD, Graeme MAGUIRE, Natalia DUARTE, Xing Li WANG and Wendy HOY

Higher CRP concentrations were associated with the following: 45–54-year age group, female subjects, the presence of skin sores, higher body mass index, waist circumference, BP, glycated haemoglobin and greater albuminuria. CRP concentrations increased with the number of cardiovascular risk factors, carotid IMT and albuminuria independently of other risk factors. These CRP concentrations were markedly higher than described in other community settings and are probably related, in a large part, to chronic and repeated infections.Their association with markers of cardiovascular risk and renal disease are compatible with the high rates of cardiovascular and renal disease in this community, and provide more evidence of strong links between these conditions, through a shared background of infection/inflammation

How much is Ms A.Y’s RELATIVE risk of CVD increased?

A) 20%

• B) 50%

• C) 100%

• D) 200%

• E) More than 200%

How much is Ms A.Y’s RELATIVE risk of CVD increased? The case for “D-E”

Del Rincon (n=236) CV events (95% CI)

Age- and sex-adjusted 3.96 (1.86–8.43)

After adjusting for CV risk factors using Poisson regression

3.17 (1.33–6.36)

Del Rincón I, et al. Arthritis Rheum 2001; 44:2737–2745; 2.

Ms A.Y.• Ms A.Y is commenced on anti-TNF alpha therapy for her rheumatological

condition.

More questions concerning Ms A.Y.• Ms A.Y is commenced on anti-TNF alpha therapy for her rheumatological

condition.

• Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF therapy (Adalimumab (Humira))?

A) LDL particle number B) HDL-C C) TG D) LDL-C E) Lp (a)

• Evidence suggests this treatment improves A) Vascular reactivity B) CVD morbidity C) Both A and BD) All aspects of the lipid profile

• Is folic acid therapy warranted in order to reduce homocysteine? Yes / No

• Do statins and Humira have identical effects on lipids and CVD risk? Yes / No

Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF

therapy (Adalimumab (Humira))? (2 correct answers)

• A) LDL particle size

• B) HDL-C

• C) TG

• D) LDL-C

• E) Lp (a)

Which of the following lipids or lipoproteins is NOT likely to increase in response to anti-TNF

therapy (Adalimumab (Humira))? The case for “E”

Lipids and Cardiovascular Risk in Rheumatoid ArthritisIncreases from baseline in mean total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, and apolipoprotein A1 and B levels -- unlike typical dyslipidemia (increased LDL and decreased HDL) -- were observed within 6 weeks of treatment initiation. These levels persisted to week 24 in patients treated with TCZ. Concurrent substantial reductions from baseline in mean levels of several inflammatory biomarkers, including C-reactive protein (CRP), serum amyloid A (SAA), haptoglobin, and lipoprotein(a), were also observed in patients treated with TCZ.

Evidence suggests this treatment improves

• A) Vascular reactivity

• B) CVD morbidity

• C) Both A and B

• D) All aspects of the lipid profile

Evidence suggests this treatment improvesThe case for “B”. No data on “A”

Anti-TNF Use Linked to Cardiovascular-Disease Drop in RAMITCHEL L. ZOLERIn both studies, treatment with an anti-TNF agent was linked to a statistically significant cut in cardiovascular (CV) events of about 50%.These results support another recent, similar finding reported in June at the Annual European Congress of Rheumatology in London. In that study, analysis of medical records from more than 109,000 U.S. patients with RA showed that every 6 months of treatment with an anti-TNF drug reduced the rate of CV events by 13%, compared with RA patients who did not receive a TNF blocker.

mailto:[email protected]

http://www.rheumatologynews.com/index.php?id=8821&tx_ttnews%5Btt_news%5D=134429&cHash=c8bfb3814c8fa60e8f858743f8ddaa17

Is folic acid therapy warranted in order to reduce homocysteine?

• Yes

• No

Is folic acid therapy warranted in order to reduce homocysteine?

The “State of Play” favours “No”

Do statins and Humira have identical effects on lipids and CVD risk?

• Yes

• No

Do statins and Humira have identical effects on lipids and CVD risk?

The case for “No”

Ann Rheum Dis 2007;66:1503-1507 Modulation of lipoprotein plasma concentrations during long-term anti-TNF therapy in patients with active rheumatoid arthritisPopa C et al

During therapy, the changes in disease activity and inflammatory status were inversely correlated with changes in plasma total and HDL cholesterol levels and positively correlated with the variation of atherogenic index.

The grey zone: What to do for the “intermediate risk” patient?

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