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Primary Prevention of Cardiovascular
Disease - Connecting Guidelines to
Local Practice
(Case Based Approach)
PRESENTED BY:...
Dr Chuang Hsuan-Hung
Cardiologist
Director of Heart Failure
Medical Director
Dr Stanley Chia
Cardiologist
Director of Inte...
Complete Cardiology Services @ AHVC
✓ General & preventive cardiology services
✓ Interventional cardiology services
✓ Valv...
GP Referral
The Lipid Problem - Case Based Approach
! Whats in the New Guidelines 2016?
! How to Treat
! How to achieve target?
! Role...
8
Clear Cardiovascular Benefits of
Aggressive Lipid-Lowering Therapy
LDL-C (mg/dl)
Events*(%)
Presentation of independent ...
9
Is Lower Better ?

How Low is low enough?
With CHD
event
(%)
50
(1.3)
70
(1.8)
90
(2.3)
110
(2.8)
130
(3.4)
150
(3.9)
17...
50% of patients in Asia are not reaching their
cholesterol targets
Cholesterol goal attainment (percent of patients attain...
Cases
Case 1
!50 year Male Lawyer
!Health Screening, Asymptomatic
!CVRF: Smoker, Positive family history of CAD
!Request for Fas...
Case 1
What is your next step?
!A. Lifestyle modification
!B. Start a statin
!C. Advice patient to do a calcium
score
Case 1
!I will do a calcium score for this patient
!Why?
!There is a strong family history of CAD
and patient is a smoker....
LCA
CAC Scoring - What it means
! In multiple studies the following definitions have been used
to correlate the CAC score and ...
Five-Year Mortality Rates in Framingham Risk Subsets by
Coronary Calcium Score
Shaw et al. Radiology 2003; 228:826-833
*
*...
Case 1
!50 year old Male Lawyer
!Health Screening, Asymptomatic
!CVRF: Smoker, Positive family history of CAD
!Request for...
Case 1
!What drug would you start?
!A. Simvastatin 40mg ON
!B. Atorvastatin 20mg ON
!C. Fenofibrate 100mg OM
ACC/AHA guidelines recommend moderate- or 

high-intensity statin in four statin benefit groups
Clinical ASCVD

CHD, strok...
ACC/AHA 2013 guidelines specify statin doses
High-intensity 

↓ LDL-C by ≥50%
Moderate-intensity ↓
LDL-C by 30–50%
Low-int...
Publication: Eur Heart J Online 27 August 2016

http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw...
Lipid targets: Summary
Level of
risk
Primary target Secondary target
Very high LDL-C <70 mg/dL (1.8 mmol/L)

Or ≥50% ↓ if ...
Case 1
!Patient came back in 4 weeks and complained
about myalgia
!?? Statin Intolerance
!Repeat Fasting Lipids
! LDL 2.40...
What is Statin Intolerance?
When a patient is unable to continue to use a statin,
either because of the development of a s...
David H F et al. Circulation 2015; 131: e389-e391
The most common presentation of statin
intolerance includes muscle aches, pains,
weakness, or cramps, often called myalgia...
Potential Mechanisms of Statin-Induced Myopathy
and Rhabdomyolysis
THEORY 1:Blocking cholesterol synthesis reduces cholest...
Statins Associated Myopathy (SAM)
! Myalgia: normal CK
! Myositis: CK 3-10 ULN
! Myopathy: CK>10x ULN
! Rhabdomyolysis:
de...
SAM prevalence
! RCT (but lead-in period: withdrawal if SAM)
!Myalgia <3%
!Myositis <0.1%
!Myopathy < 0.01%
!Rhabdo very r...
Case 1
!What is the next step?
!I stopped the Lipitor and reviewed him in 2 week
!Repeat CK
!CK 1045 U/L (20-192)
!What is...
Case 2
!60/Female
!CVRF: Newly diagnosed DM
!Routine screening for risk factors
!Fasting Lipids
! LDL 3.00 mmol/L
! HDL 0....
Case 2
!10 year ASCVD risk: 8.3%
!What is your next step?
!A. Lifestyle modification
!B. Start a statin
!C. Advice patient...
ADA 2016 guidelines
■ 2016 ADA guidelines recommend:
⬥ high-intensity statins for all diabetic patients aged 40-75 years
w...
*At baseline MI=myocardial infarction
P<0.001 for prior MI vs. no prior MI and for diabetes vs.
no diabetes
7-Year Inciden...
Case 2
!What is your drug of choice?
!A. Simvastatin 40mg ON
!B. Atorvastatin 20mg ON
Fasting Lipids
! LDL 3.00 mmol/L
! H...
NICE lipid guidelines: statin intensity categories are based
on LDL-cholesterol reduction
39
Statin LDL-cholesterol reduct...
Case 3
!40 year old Male Marathon runner
!Recently was found to have severe
hypercholesterolaemia (LDL=6.0 mmol/l)
!Histor...
Case 3
• Will you proceed with the plan to commence statin?
Yes / No
• If you proceed, what drug and what dosage level wil...
Will you proceed with the plan to commence statin?
Br J Clin Pharmacol. 2004 April; 57(4): 525–528.
Professional athletes ...
Non-statin therapy is limited only to individuals with
insufficient response to statin therapy
■ Non-statin therapy is not...
THANK YOU!

ANY QUESTIONS?
www.ahvc.com.sg
Case 4
!65/Male
!CVRF: Smoker, Hyperlipidaemia
!Recent PCI for symptomatic CAD
!Fasting Lipids
! LDL 2.95 mmol/L
! HDL 0.9...
Case 4
What is your drug of choice?
!A. Atorvastatin 20mg ON
!B. Ezetrol 10mg OM
!C. Niaspan 1g OM
AHVC 2014
Case 4
! On follow-up, Lipid trend as shown:
! Fasting Lipids
! Jul 13 Dec 13 June 14
! LDL 2.85 3.45 3.60 mmol/L
! HDL 0....
Case 4
! What will you do next?
! A. Atorvastatin 40 mg ON
! B. Rosuvastatin 20 mg ON
! C. Vytorin 10/20 OM
CAC Scoring 0.7-1.0 mSv
CTCA 1.1-4 mSv
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice
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Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice

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Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice

  1. 1. Primary Prevention of Cardiovascular Disease - Connecting Guidelines to Local Practice (Case Based Approach) PRESENTED BY: DR JEREMY CHOW MBBS, MRCP (UK), MRCP (London), M Med (Int Med) FAMS, FESC, FHRS Certified Cardiac Device Specialist Consultant Cardiologist & Electrophysiologist Director of Electrophysiology Service Email: drchow.jeremy@asianheart.com.sg www.ahvc.com.sg
  2. 2. Dr Chuang Hsuan-Hung Cardiologist Director of Heart Failure Medical Director Dr Stanley Chia Cardiologist Director of Interventional Cardiology Service Deputy Medical Director Dr Tan Chong Hiok Cardiologist Co-Director of Interventional Cardiology Service Dr Goh Ping Ping Cardiologist, Echocardiologist Clinical Exercise Specialist Director of Cardiovascular Imaging Service Dr Jeremy Chow Cardiologist, Electrophysiologist Director of Electrophysiology Service Dr Kenneth Guo Cardiologist, Echocardiologist Director of Adult Congenital Heart Disease Service
  3. 3. Complete Cardiology Services @ AHVC ✓ General & preventive cardiology services ✓ Interventional cardiology services ✓ Valvular heart disease services ✓ Heart failure & mechanical cardiac support services ✓ Electrophysiology services ✓ Adult congenital heart diseases management ✓ Sports Cardiology
  4. 4. GP Referral
  5. 5. The Lipid Problem - Case Based Approach ! Whats in the New Guidelines 2016? ! How to Treat ! How to achieve target? ! Role of Statins vs non Statins ! PCSK9 ! Statins Intolerant?
  6. 6. 8 Clear Cardiovascular Benefits of Aggressive Lipid-Lowering Therapy LDL-C (mg/dl) Events*(%) Presentation of independent noncomparative trials with different patient populations *Event rates for HPS, CARE, and LIPID are for death from CHD and nonfatal MI. Event rates for 4S and TNT also include resuscitation after 
 cardiac arrest. CARE=Cholesterol and Recurrent Events; CHD=coronary heart disease; HPS=Heart Protection Study; LIPID=Long-Term Intervention with
 Pravastatin in Ischemic Disease; TNT=Treating to New Targets; 4S=Scandinavian Simvastatin Survival Study Adapted from LaRosa JC et al N Engl J Med 2005;352(14):1425–1435. Statin Placebo 0 30 0 110 170 210 25 20 15 10 5 13090 150 190 4S
 Study 70 CARE
 Study TNT (atorvastatin 80 mg) 4S
 Study LIPID
 Study CARE
 Study HPS
 Study LIPID
 Study HPS
 Study TNT (atorvastatin 10 mg)
  7. 7. 9 Is Lower Better ?
 How Low is low enough? With CHD event (%) 50 (1.3) 70 (1.8) 90 (2.3) 110 (2.8) 130 (3.4) 150 (3.9) 170 (4.4) 190 (4.9) 210 (5.4) 0 5 10 15 20 25 TNT 80 mg TNT 10 mg Lipid-Rx CARE-PlCARE-Rx 4S-Rx Lipid-Pl TNT Entry 4S-Pl AFCAPS-Rx WOS-Rx WOS-Pl AFCAPS-Pl LDL-cholesterol [mg/dL (mmol/L)] Secondary prevention Primary prevention LDL 2.0 LDL 1.5?
  8. 8. 50% of patients in Asia are not reaching their cholesterol targets Cholesterol goal attainment (percent of patients attaining goal) by risk status in the overall population and by country/ region ➢ REALITY-Asia Study: To evaluate prescribing patterns and cholesterol goal attainment in the ‘real world’ setting (N=2622)
  9. 9. Cases
  10. 10. Case 1 !50 year Male Lawyer !Health Screening, Asymptomatic !CVRF: Smoker, Positive family history of CAD !Request for Fasting Lipids ! LDL 4.20 mmol/L ! HDL 0.76 mmo/L ! TG 1.80 mmol/L
  11. 11. Case 1 What is your next step? !A. Lifestyle modification !B. Start a statin !C. Advice patient to do a calcium score
  12. 12. Case 1 !I will do a calcium score for this patient !Why? !There is a strong family history of CAD and patient is a smoker. !Calcium score will aid in the diagnosis of atherosclerosis and hence management plan.
  13. 13. LCA
  14. 14. CAC Scoring - What it means ! In multiple studies the following definitions have been used to correlate the CAC score and the coronary plaque burden:
 !0 No identifiable disease
 !1 – 99 Mild Disease
 !100 – 399 Moderate Disease
 !>400 Severe Disease
  15. 15. Five-Year Mortality Rates in Framingham Risk Subsets by Coronary Calcium Score Shaw et al. Radiology 2003; 228:826-833 * * * *p<0.001
  16. 16. Case 1 !50 year old Male Lawyer !Health Screening, Asymptomatic !CVRF: Smoker, Positive family history of CAD !Request for Fasting Lipids ! LDL 4.20 mmol/L ! HDL 0.76 mmo/L ! TG 1.80 mmol/L !Calcium score 350
  17. 17. Case 1 !What drug would you start? !A. Simvastatin 40mg ON !B. Atorvastatin 20mg ON !C. Fenofibrate 100mg OM
  18. 18. ACC/AHA guidelines recommend moderate- or 
 high-intensity statin in four statin benefit groups Clinical ASCVD
 CHD, stroke, and 
 peripheral arterial disease, all of presumed atherosclerotic origin Diabetes mellitus 
 + age 40–75 years 
 + LDL-C 70–189 mg/dL (1.8–4.9 mmol/L) ASCVD risk ≥7.5% No diabetes
 + age 40–75 years 
 + LDL-C 70–189 mg/dL (1.8–4.9 mmol/L) LDL-C 
 ≥190 mg/dL
 (~5 mmol/L) High-intensity statin* High-intensity statin* Moderate- or high-intensity statin† Moderate- or high-intensity statin‡ *Moderate intensity for selected patients †High intensity if ASCVD risk ≥7.5% ‡Choice according to individual patient factors ACC/AHA, American College of Cardiology and American Heart Association ASCVD, atherosclerotic cardiovascular disease Stone NJ, et al. J Am Coll Cardiol 2014;63:2889–2934
  19. 19. ACC/AHA 2013 guidelines specify statin doses High-intensity 
 ↓ LDL-C by ≥50% Moderate-intensity ↓ LDL-C by 30–50% Low-intensity 
 ↓ LDL-C by <30%* Atorvastatin (40)–80 mg 10–20 mg – Rosuvastatin 20–40 mg 5–10 mg – Simvastatin – 20–40 mg 10 mg Pravastatin – 40–80 mg 10–20 mg Lovastatin – 40 mg 20 mg Fluvastatin XL – 80 mg – Fluvastatin – 40 mg bid 20–40 mg Pitavastatin – 2–4 mg 1 mg Bold: Statins and doses evaluated in RCTs Italics: Statins and doses approved by US FDA but not tested in RCTs reviewed *Should be used in patients unable to tolerate moderate-to high-intensity therapy Asian ancestry may modify the statin dose prescribed 23Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print
 Reproduced with kind permission from American College of Cardiology Jan 2014
  20. 20. Publication: Eur Heart J Online 27 August 2016
 http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw272
  21. 21. Lipid targets: Summary Level of risk Primary target Secondary target Very high LDL-C <70 mg/dL (1.8 mmol/L)
 Or ≥50% ↓ if baseline 70−135 mg/dL
 (1.8−3.5 mmol/L) Non-HDL-C <100 mg/ dL (2.6 mmol/L)
 Or ApoB <80 mg/dL High LDL-C <100 mg/dL (2.6 mmol/L)
 Or ≥50% ↓ if baseline 100−200 mg/dL (1.8−3.5 mmol/L) Non-HDL-C <130 mg/ dL (3.4 mmol/L)
 Or ApoB <100 mg/dL Moderate LDL-C <115 mg/dL (3.0 mmol/L) Non-HDL-C <145 mg/ dL (3.8 mmol/L) Low LDL-C <115 mg/dL (3.0 mmol/L) Non-HDL-C <145 mg/ dL
 (3.8 mmol/L) 25 Publication: Eur Heart J Online 27 August 2016
 http://eurheartj.oxfordjournals.org/content/early/2016/08/26/eurheartj.ehw272
  22. 22. Case 1 !Patient came back in 4 weeks and complained about myalgia !?? Statin Intolerance !Repeat Fasting Lipids ! LDL 2.40 mmol/L ! HDL 1.06 mmo/L ! TG 1.50 mmol/L !CK 245 U/L (20-192)
  23. 23. What is Statin Intolerance? When a patient is unable to continue to use a statin, either because of the development of a side effect or because of evidence on a blood test that certain markers of liver function or muscle function (creatine kinase) are sufficiently abnormal to cause concern. The intolerance can be either partial (ie, only some statins at some doses) or complete (ie, all statins at any dose). David H F et al. Circulation 2015; 131: e389-e391
  24. 24. David H F et al. Circulation 2015; 131: e389-e391
  25. 25. The most common presentation of statin intolerance includes muscle aches, pains, weakness, or cramps, often called myalgia; these can occur in up to 15% of treated patients.
  26. 26. Potential Mechanisms of Statin-Induced Myopathy and Rhabdomyolysis THEORY 1:Blocking cholesterol synthesis reduces cholesterol content of skeletal muscle membranes, making them unstable THEORY 2: Statins lead to a reduced synthesis of ubiquinone (coenzyme Q10), an essential element of mitochondria, thereby disturbing normal cell respiration THEORY 3: Reduction of small GTP-binding proteins leads to muscle apoptosis Pasternak RC et al. J Am Coll Cardiol. 2002;40:567-572 Thompson PD et al. JAMA. 2003;289:1681-1690
  27. 27. Statins Associated Myopathy (SAM) ! Myalgia: normal CK ! Myositis: CK 3-10 ULN ! Myopathy: CK>10x ULN ! Rhabdomyolysis: definitions vary ! CK>10x ULN with renal impairment and need for redydration ! CK>10xULN with myoglobinaemia, myoglobinuria
  28. 28. SAM prevalence ! RCT (but lead-in period: withdrawal if SAM) !Myalgia <3% !Myositis <0.1% !Myopathy < 0.01% !Rhabdo very rare (placebo = statin) ! Clinical practice: COMMON !PRIMO trial of French GPs (Bruckert et al) !High dose statins ! up to 17% SAM
  29. 29. Case 1 !What is the next step? !I stopped the Lipitor and reviewed him in 2 week !Repeat CK !CK 1045 U/L (20-192) !What is the problem now?
  30. 30. Case 2 !60/Female !CVRF: Newly diagnosed DM !Routine screening for risk factors !Fasting Lipids ! LDL 3.00 mmol/L ! HDL 0.56 mmo/L ! TG 1.90 mmol/L
  31. 31. Case 2 !10 year ASCVD risk: 8.3% !What is your next step? !A. Lifestyle modification !B. Start a statin !C. Advice patient to do a calcium score
  32. 32. ADA 2016 guidelines ■ 2016 ADA guidelines recommend: ⬥ high-intensity statins for all diabetic patients aged 40-75 years with ASCVD risk factors ⬥ moderate-intensity statins for all diabetics aged >40 years with no ASCVD risk factors ■ Moderate-intensity statin therapy may be considered if a patient cannot tolerate high intensity statin therapy ■ The addition of ezetimibe to moderate-intensity statin therapy has been shown to provide additional cardiovascular benefit compared with moderate-intensity statin therapy alone 36 Chamberlain JJ, Rhinehart AS, Shaefer CF Jr, Neuman A. Diagnosis and Management of Diabetes: Synopsis of the 2016 American Diabetes Association Standards of Medical Care in Diabetes. Ann Intern Med. 2016 Apr 19;164(8):542-52.
  33. 33. *At baseline MI=myocardial infarction P<0.001 for prior MI vs. no prior MI and for diabetes vs. no diabetes 7-Year Incidence of Fatal and Nonfatal MI 4% 19% 45% Prior MI Nondiabetic Diabetic (n=1,373) (n=1,059) No Prior MI* Prior MI No Prior MI* 20% Haffner SM, et al. N Eng J Med. 1998;339:229-234.
  34. 34. Case 2 !What is your drug of choice? !A. Simvastatin 40mg ON !B. Atorvastatin 20mg ON Fasting Lipids ! LDL 3.00 mmol/L ! HDL 0.56 mmo/L ! TG 1.90 mmol/L
  35. 35. NICE lipid guidelines: statin intensity categories are based on LDL-cholesterol reduction 39 Statin LDL-cholesterol reduction Dose (mg/day) 5 10 20 40 80 Fluvastatin – – 21%1 27%1 33%2 Pravastatin – 20%1 24%1 29%1 – Simvastatin – 27%1 32%2 37%2 42%3§ Atorvastatin – 37%2 43%3 49%3 55%3 Rosuvastatin 38%2 43%3 48%3 53%3 – 1 20–30% reduction in LDL-C: low-intensity statin
 2 31–40% reduction in LDL-C: medium-intensity statin
 3 >40% reduction in LDL-C: high-intensity statin (atorva 20, 40 or 80 mg) 
 § Advice from UK Medicines and Healthcare products Regulatory Agency (MHRA). There is an increased risk of myopathy associated with high-dose (80 mg) simvastatin. The 80 mg dose should be considered only in patients with severe hypercholesterolemia and high risk of cardiovascular complications who have not achieved their treatment goals on lower doses, when the benefits are expected to outweigh the potential risks The information used to make the table is from Law MR et al BMJ 2003;326:1423 National Institute for Health and Care Excellence
 Lipid modification July 2014 http://www.nice.org.uk/Guidance/CG181
  36. 36. Case 3 !40 year old Male Marathon runner !Recently was found to have severe hypercholesterolaemia (LDL=6.0 mmol/l) !History is consistent with Familial Hypercholesterolaemia. !You plan to start statin therapy…. BUT !His baseline CK levels often exceed 500 IU/l, but it has not been possible to avoid exercise before collection. !So What should we do?
  37. 37. Case 3 • Will you proceed with the plan to commence statin? Yes / No • If you proceed, what drug and what dosage level will you use? • A) Moderate potency statin • B) High potency statin • C) Vytorin?
  38. 38. Will you proceed with the plan to commence statin? Br J Clin Pharmacol. 2004 April; 57(4): 525–528. Professional athletes suffering from familial hypercholesterolaemia rarely tolerate statin treatment because of muscular problems H Sinzinger and J O'Grady* Muscular problems are the major group of side-effects during statin treatment. They are known to occur much more frequently during and after exercise. For the last 8 years we have monitored 22 professional athletes in whom, because of familial hypercholesterolaemia, treatment with different statins was attempted. Only six out of the 22 finally tolerated at least one member of this family of drugs. In three of these six the first statin prescribed allowed training performance without any limitation. Changing the drug demonstrated that only two tolerated all the four or five statins examined (atorvastatin, fluvastatin, lovastatin, pravastatin, simvastatin). These findings indicate that in top sports performers only about 20% tolerate statin treatment without side-effects. Clinical decision making as to lipid lowering therapy thus becomes a critical issue in this small subgroup of patients
  39. 39. Non-statin therapy is limited only to individuals with insufficient response to statin therapy ■ Non-statin therapy is not recommended for routine therapy ■ Benefit groups should receive maximum tolerated intensity of statin ■ Adherence to lifestyle and to statin therapy should be re- emphasized before the addition of a non-statin drug is considered Insufficient response to 
 high-intensity statin (LDL-C reduction <50%) Re-emphasize adherence to healthy lifestyle and statin Consider addition of non-statin cholesterol-lowering drug(s) • Preferably drug shown to ↓ ASCVD in RCTs • And if benefit of ASCVD ↓ outweighs the potential AEs Insufficient response to 
 moderate-intensity statin 
 (LDL-C reduction <30%) Re-emphasize adherence to healthy lifestyle and statin ↑ statin dose (if needed) Consider non-statin monotherapy only if patient is completely statin-intolerant Stone NJ, et al. J Am Coll Cardiol 2013 Nov 7. Epub ahead of print 43
  40. 40. THANK YOU!
 ANY QUESTIONS? www.ahvc.com.sg
  41. 41. Case 4 !65/Male !CVRF: Smoker, Hyperlipidaemia !Recent PCI for symptomatic CAD !Fasting Lipids ! LDL 2.95 mmol/L ! HDL 0.96 mmo/L ! TG 1.50 mmol/L
  42. 42. Case 4 What is your drug of choice? !A. Atorvastatin 20mg ON !B. Ezetrol 10mg OM !C. Niaspan 1g OM
  43. 43. AHVC 2014
  44. 44. Case 4 ! On follow-up, Lipid trend as shown: ! Fasting Lipids ! Jul 13 Dec 13 June 14 ! LDL 2.85 3.45 3.60 mmol/L ! HDL 0.96 1.00 1.05 mmo/L ! TG 1.50 1.90 1.80 mmol/L
  45. 45. Case 4 ! What will you do next? ! A. Atorvastatin 40 mg ON ! B. Rosuvastatin 20 mg ON ! C. Vytorin 10/20 OM
  46. 46. CAC Scoring 0.7-1.0 mSv CTCA 1.1-4 mSv

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