RECENT LIPID GUIDELINES UPDATE. HELPFUL FOR PHYSICIANS AND CARDIOLOGIST, DIABETOLOGIST, PEDIATRICIANS

1. LATEST LIPID
GUIDELINES
PRESENTER- SATYA PRASAD MAHAPATRA
MODERATOR- PROF DR SATYENDRA TEWARI

2. OVERVIEW
• ESC Guidelines
• AHA/ACC Guidelines
• LAI Guidelines
• Comparison of Current guidelines
• Conclusion
• References

3. ESC GUIDELINES

4. CHOLESTEROL AS A CV RISK FACTOR
• The role of LDL-C and other apo-B-containing lipoproteins in the development of ASCVD
has been demonstrated by genetic, observational, and interventional studies.
• Prolonged lowering of LDL-C is associated with lower risk of ASCVD, throughout the
range studied
• The relative reduction in CVD risk is proportional to the absolute size of the change in
LDL-C, irrespective of the drugs used to achieve such change.
Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, Hegele RA, Krauss RM, Raal FJ, Schunkert H, Watts GF, Boren J, Fazio S, Horton JD,
Masana L, Nicholls SJ, Nordestgaard BG, van de Sluis B, Taskinen MR, Tokgozoglu L, Landmesser U, Laufs U, Wiklund O, Stock JK, Chapman MJ, Catapano
AL. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus
statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017;38:24592472.
Cholesterol Treatment Trialists’ (CTT) Collaboration, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J,
Collins R. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
Lancet 2010;376:1670􏰀1681.
Cholesterol Treatment Trialists’ (CTT) Collaborators, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, Voysey M, Gray A, Collins R,
Baigent C. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27
randomised trials. Lancet 2012;380:581590.

5. • The relationship between non-HDL-C and CV risk is as strong as the relationship
with LDL-C.
• HDL-C is inversely associated with CVD risk, however, very high HDL-C levels may
signal an increased CVD risk.
• There is no evidence from Mendelian randomization studies or randomized trials
of cholesteryl ester transfer protein inhibitors, that raising plasma HDL-C reduces
CVD risk.
Pencina KM, Thanassoulis G, Wilkins JT, Vasan RS, Navar AM, Peterson ED, Pencina MJ, Sniderman AD. Trajectories of Non-
HDL Cholesterol Across Midlife: Implications for Cardiovascular Prevention. J Am Coll Cardiol2019;74:70􏰀79.
Holmes, Michael V., et al. "Mendelian randomization of blood lipids for coronary heart disease." European heart journal 36.9
(2015): 539-550.

6. Cardiovascular disease risk classification ESC 2021
• 2016 & 2019 ESC prevention guidelines:- Systemic Coronary Risk Estimation (SCORE) algorithm was
used to estimate 10-year risk of CVD death.
• CVD morbidity (non-fatal myocardial infarction, non-fatal stroke) combined with CVD mortality better
reflects the total burden of ASCVD.
• SCORE-2 estimates an individual’s 10-year risk of fatal and non-fatal CVD events (myocardial infarction,
stroke) in apparently healthy people aged 40-69 years with risk factors that are untreated or have been
stable for several years.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, Chapman MJ, De Backer GG, Delgado V, Ference BA, Graham IM.
2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Atherosclerosis.
2019 Nov 1;290:140-205.
"SCORE2 risk prediction algorithms: new models to estimate 10-year risk of cardiovascular disease in Europe." European
heart journal 42, no. 25 (2021): 2439-2454.

7. Step-wise Approach to CVD Prevention

10. Risk regions-
SCORE2-OP working group and ESC Cardiovascular risk collaboration. SCORE2-OP risk prediction algorithms: estimating incident
cardiovascular event risk in older persons in four geographical risk regions. Eur Heart J 2021;42:24552467

11. CARDIOVASCULAR RISK CATEGORIES BASED ON
SCORE-2/SCORE-2-OP
• In all age groups,
consideration of Risk
modifiers, lifetime CVD risk,
treatment benefit, co-
morbidities, frailty and
patient preferences must be
considered before treatment
decisions.
• (a)In apparently healthy
people >_70 years old, the
treatment recommendation
for lipid-lowering drugs is
Class IIb (‘may be
considered’).
Pennells, Lisa, et al. "Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-analysis of 86 prospective studies."
European heart journal 40.7 (2019): 621-631.

13. • SCORE-2 charts do not apply to:-
1. Persons with documented CVD
2. DM
3. Familial Hypercholesterolemia
4. Other genetic or rare lipid disorders
5. CKD
6. Pregnant women.
Pennells, Lisa, et al. "Equalization of four cardiovascular risk algorithms after systematic recalibration: individual-participant meta-
analysis of 86 prospective studies." European heart journal 40.7 (2019): 621-631.

14. OLDER POPULATION
• The gradient of the relationship between classical risk factors, such as lipids and
BP with CVD risk attenuates with age.
• Risk for non-CVD mortality increases (‘competing risk’)
• SCORE-2-OP algorithm estimates 5-year and 10-year fatal and non- fatal CVD
events (myocardial infarction, stroke) adjusted for competing risks in apparently
healthy people aged >70 years.
SCORE2-OP working group and ESC Cardiovascular risk collaboration. SCORE2-OP risk prediction algorithms: estimating incident cardiovascular
event risk in older persons in four geographical risk regions. Eur Heart J 2021;42:24552467.
Berry SD, Ngo L, Samelson EJ, Kiel DP. Competing risk of death: an important consideration in studies of older adults. J Am Geriatr Soc
2010;58:783787

15. APPARENTLY HEALTHY 50-69 year age group
• Smoking cessation, lifestyle recommendations and SBP <160 are recommended
for all.
• Very High Risk:- 10 year CVD > 10%:- treatment of CVD risk factors is
recommended
• High Risk:- 5-<10%:- treatment of Risk factors should be considered
• Low-Moderate risk:- <5%:- Risk factor treatment not recommended, unless RISK
MODIFIERS+ or estimated lifetime risk and treatment benefit is considered
substantial.
Jaspers NEM, Blaha MJ, Matsushita K, van der Schouw YT, Wareham NJ, Khaw KT, Geisel MH, Lehmann N, Erbel R, Jockel KH, van der Graaf Y,
Verschuren WMM, Boer JMA, Nambi V, Visseren FLJ, Dorresteijn JAN. Prediction of individualized lifetime benefit from cholesterol lowering,
blood pressure lowering, antithrombotic therapy, and smoking cessation in apparently healthy people. Eur Heart J 2020;41:11901199.

16. APPARENTLY HEALTHY > 70 years of age
• Smoking cessation, lifestyle recommendations and SBP <160 are recommended for all.
• Very High Risk:- 10 year CVD > 15%:- treatment of CVD risk factors is recommended
• High Risk:- 7.5-<15%:- treatment of Risk factors should be considered
• Low-Moderate risk:- <7.5%:- Risk factor treatment not recommended, unless RISK
MODIFIERS+ or estimated lifetime risk and treatment benefit is considered substantial.
Berkelmans GFN, Gudbjornsdottir S, Visseren FLJ, Wild SH, Franzen S, Chalmers J, Davis BR, Poulter NR, Spijkerman AM, Woodward M, Pressel
SL, Gupta AK, van der Schouw YT, Svensson AM, van der Graaf Y, Read SH, Eliasson B, Dorresteijn JAN. Prediction of individual life-years gained
without cardiovascular events from lipid, blood pressure, glucose, and aspirin treatment based on data of more than 500 000 patients with
Type 2 diabetes mellitus. Eur Heart J 2019;40:28992906
Benetos A, Petrovic M, Strandberg T. Hypertension Management in Older and Frail Older Patients. Circ Res 2019;124:10451060.

17. APPARENTLY HEALTHY < 50 years of age
• Smoking cessation, lifestyle recommendations and SBP <160 are recommended for all.
• Very High Risk:- 10 year CVD > 7.5%:- treatment of CVD risk factors is recommended
• High Risk:- 2.5-<7.5%:- treatment of Risk factors should be considered
• Low-Moderate risk:- <2.5%:- Risk factor treatment not recommended, unless RISK
MODIFIERS+ or estimated lifetime risk and treatment benefit is considered substantial.
Ference BA, Bhatt DL, Catapano AL, Packard CJ, Graham I, Kaptoge S, Ference TB, Guo Q, Laufs U, Ruff CT, Cupido A, Hovingh GK, Danesh J,
Holmes MV, Smith GD, Ray KK, Nicholls SJ, Sabatine MS. Association of Genetic Variants Related to Combined Exposure to Lower Low-Density
Lipoproteins and Lower Systolic Blood Pressure With Lifetime Risk of Cardiovascular Disease. JAMA 2019;322:13811391

18. POTENTIAL RISK MODIFIERS
• Psychosocial stress:-
1. RR=1.2-2.0
2. Optimism and a strong sense of purpose are associated with a lower risk
• Ethnicity:-
1. South Asian:- Multiply the risk by 1.3 for Indians and Bangladeshis; 1.7 for Pak
2. Other Asians:- 1.1
3. Black Caribbean:- 0.85
4. Black African and Chinese:- 0.7
Albus, C., et al. "Significance of psychosocial factors in cardiology—Update 2018: Position paper of the German Cardiac
Society." Der Kardiologe 12 (2018): 312-331.
Kim, Jae-Min, et al. "Long-term cardiac outcomes of depression screening, diagnosis and treatment in patients with acute
coronary syndrome: the DEPACS study." Psychological medicine 51.6 (2021): 964-974.

19. • Coronary Artery Calcium:-
Higher than expected CAC increases
person’s calculated risk
Peters, Sanne AE, et al. "Improvements in risk
stratification for the occurrence of cardiovascular
disease by imaging subclinical atherosclerosis: a
systematic review." Heart (2011).
Lin, Jennifer S., et al. "Nontraditional risk factors in
cardiovascular disease risk assessment: updated
evidence report and systematic review for the US
Preventive Services Task Force." Jama 320.3 (2018): 281-
297.

21. ESTABLISHED ASCVD (Secondary Prevention)
• Very high risk of recurrent CVD events, if risk factors are not treated.
• STEP 1:- All 4
• Stop smoking and lifestyle recommendations
• LDL-C > 50% reduction + < 70 mg/dl
• SBP <140—130 mm HG
• Anti-thrombotic therapy
• STEP 2:- Mandatory, after completion of Step 1, for intensified goals
Based on 10 year CVD risk, lifetime CVD risk, Co-morbidities, Frailty and patient
preferences:- SBP <130 + LDL-C< 55 + DAPT/ other interventions

22. RISK STRATIFICATION TOOLS FOR SECONDARY PREVENTION
• SMART:- Secondary Manifestations of Arterial Diseases risk score:- 10 year CVD
risk
• EUROASPIRE risk model:- Estimates 2 year risk of recurrent CVD in patients with
stable CVD
• LIFE-CVD:- Lifetime CV risk
Kaasenbrood, Lotte, et al. "Distribution of estimated 10-year risk of recurrent vascular events and residual risk in a secondary
prevention population." Circulation 134.19 (2016): 1419-1429.
De Bacquer, Dirk, et al. "Prediction of recurrent event in patients with coronary heart disease: the EUROASPIRE risk model:
results from a prospective study in 27 countries in the WHO European region-the EURObservational research programme
(EORP) of the European society of cardiology (ESC)." European Journal of Preventive Cardiology 29.2 (2022): 328-339.
Jaspers, Nicole EM, et al. "Prediction of individualized lifetime benefit from cholesterol lowering, blood pressure lowering,
antithrombotic therapy, and smoking cessation in apparently healthy people." European heart journal 41.11 (2020): 1190-
1199.

25. AHA/ACC GUIDELINES

26. ASCVD- ATHEROSCLEROTIC CARDIOVASCULAR DISEASE RISK
• Clinical ASCVD:-
• ACS/ Old MI/ CSA/ UA/ P-PCI
• TIA/ AIS
• PAD
• Aortic Aneurysm
• Low Risk- < 5%
• Borderline Risk- 5-<7.5%
• Intermediate Risk- 7.5-<20%
• High Risk- 20% or more
Grundy, Scott M., et al. "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood
cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines." Circulation
139.25 (2019): e1082-e1143.

27. • Very HIGH RISK:-
• History of Multiple Major ASCVD events (or)
• 1 Major ASCVD event + Multiple High Risk Conditions.

28. PRIMARY PREVENTION
LDL-C
>190 mg/dl
High Intensity Statin(COR-1)
<190 mg/dl
Age
0-19 20-39 40-75 >75
Lifestyle Mx;
Statin, if FH
Lifestyle Mx + Statin,
if family H/o
Premature ASCVD +
LDL-160 or more
Diabetic? Yes
No
Moderate Intensity Statin(COR 1)
+ RISK assessment to consider for
High intensity statin
LDL 70-189:-
10 year ASCVD
assessment
Clinical assessment and risk
discussion
Budoff, Matthew J., et al. "Ten-year association of coronary artery
calcium with atherosclerotic cardiovascular disease (ASCVD) events: the
multi-ethnic study of atherosclerosis (MESA)." European heart journal
39.25 (2018): 2401-2408.

30. TREATMENT MONITORING
• Fasting lipid profile(Total Cholesterol, TG, HDL-C, LDL-C)
• Initially 4-12 weeks after Statin initiation or dose adjustment
• F/b every 3-12 monthly
• Thereafter, based on clinical need.
Stone, Neil J., et al. "2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report
of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines." Circulation 129.25_suppl_2 (2014): S1-S45.

31. OLDER ADULTS:- > 75 YEARS OF AGE
• LDL-C 70-189 mg/dl- Initiating a Moderate intensity Statin may be
reasonable(COR 2b)
• Reasonable to stop Statin therapy, if Physical/ Cognitive decline, frailty, multiple
morbidities or reduced life expectancy limit the potential benefits of Statin
therapy.(COR 2b)
• 76-80 years of age with LDL-C 70-189 mg/dl, CAC may be measured and those
with CAC zero to avoid Statin therapy.(COR 2b)
Teng, Monica, et al. "Statins for primary prevention of cardiovascular disease in elderly patients: systematic review
and meta-analysis." Drugs & aging 32 (2015): 649-661.

32. PATIENTS WITH DIABETES MELLITUS
• 40-75 years of age + DM:- Moderate Intensity Statin, irrespective of ASCVD(COR1)
• Adults with DM + multiple ASCVD risk factors:- High intensity Statin(COR 2a)
• DM + ASCVD >20%:- Add ezetimibe to maximally tolerated Statin dose(COR 2b)
• 20-39 years + Diabetes Specific risk enhancers:- Initiate Statin therapy(COR 2b)
Colhoun, Helen M., et al. "Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin
Diabetes Study (CARDS): multicentre randomised placebo-controlled trial." The Lancet 364.9435 (2004): 685-696.

33. SECONDARY PREVENTION
• Clinical ASCVD +
• All patients:- Lifestyle modifications
• 2 subdivisions:-
1. High Risk group
2. Very High Risk group
Very HIGH RISK group:- includes history of Multiple Major ASCVD events or 1 Major
ASCVD event + Multiple High Risk Conditions.
Grundy, Scott M., et al. "2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood
cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines." Circulation
139.25 (2019): e1082-e1143

34. HIGH RISK GROUP
• Age <75 years + Clinical ASCVD:- Initiate/ continue High Intensity Statin therapy
with an Aim of 50% or more reduction of LDL-C levels.(COR-1)
• Statin C/I or Statin associated side effects:- Moderate Intensity Statin therapy
with an aim of 30-49% reduction in LDL-C levels.(COR-1)
• Age > 75 years + Clinical ASCVD:- Initiate Moderate/ High intensity statin therapy
after discussing Risk Benefit(COR-2a)
• Clinical ASCVD + Maximally tolerated statin therapy + LDL-C > 70 mg/dl:- may be
reasonable to add Ezetimibe(COR 2b):- IMPROVE-IT TRIAL
• HFrEF(ICMP)+ reasonable life expectancy(3-5 years):- initiate Moderate intensity
Statin(COR 2b)

35. VERY HIGH RISK GROUP
• Maximally tolerate LDL-C reduction therapy includes Maximally tolerated statin +
Ezetimibe(COR 1)
• On maximally tolerated statin therapy + LDL-C >70 mg/dl:- reasonable to add
Ezetimibe(COR 2a)
• On maximally tolerated LDL-C reduction therapy(Statin+ Ezetimibe) + LDL-C >70
mg/dl or non-HDL-C > 100 mg/dl:- reasonable to add PCSK9 inhibitor(COR 2a):-
FOURIER and ODYSSEY outcomes

36. Measurement of LDL-C and Non HDL-C
• Adults 20 years of age or older:-
1. Not on lipid lowering therapy measurement of Fasting/ Non fasting Lipid
profile to estimate ASCVD risk and document baseline LDL-C (COR 1)
2. Initial non fasting TG of 400mg/dl or more repeat Fasting lipid profile(COR 1)
3. No personal H/o ASCVD, but a family H/o Premature ASCVD+ or Genetic
Hyperlipidemia measure Fasting lipid profile

37. RATIONALE FOR EXPERT CONSENSUS DECISION PATHWAY
2022
Patient population
where newer NON
STATIN therapies to be
considered?
Situations where newer
NON STATIN therapies to
be considered?
If newer therapies to be
considered, then in what
order, to maximize
benefit?
Since 2018 AHA/ACC guidelines, 3 additional non statin drugs have received FDA
approval:- Bempedoic acid, Evinacumab and Inclisiran
Writing Committee, et al. "2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol
lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Solution
Set Oversight Committee." Journal of the American College of Cardiology 80.14 (2022): 1366-1418.

38. • STEP 1:- ASSESS RESPONSE TO THERAPY
• STEP 2:- STATIN ADHERENCE
• STEP 3:- STATIN INTENSIFICATION
• STEP 4:- ADD NON STATIN THERAPY

39. Clinical ASCVD on Statin for Secondary prevention-
VERY HIGH RISK
• A lower LDL-C goal of < 55 mg/dl(Non HDL < 85) is recommended.
• Absolute LDL-C reduction is directly associated with ASCVD risk reduction.
• No LDL-C level below which benefit ceases
Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease.
N Engl J Med. 2017;376: 1713–1722.
Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl
J Med. 2015;372:2387–2397.
Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-
analysis of data from 170,000 partici- pants in 26 randomised trials. Lancet. 2010;376:1670– 1681.

40. • Ezetimibe as initial choice:-
1. < 25% additional lowering of LDL-C needed
2. Recent ACS < 3 months
3. Ease of use/ Cost
• PCSK9 mAb as initial choice:-
1. 25% additional lowering of LDL-C needed
2. 14-day/monthly s.c inj dosing schedule
3. Limitations:- Cost, Refrigeration
• Sub-optimal response:- Statin + Ezetimibe + PCSK9mAb
• Further lowering of LDL-C needed:- + Bempedoic acid/ Inclisiran may be
considered

41. Clinical ASCVD on Statin for Secondary
prevention- HIGH RISK
• Goal:- > 50% reduction in LDL-C from baseline or LDL-C < 70 mg/dl( non-HDL-C <
100 mg/dl)
• 22% proportional risk reduction for major vascular events for each 38 mg/dl
reduction in LDL-C
Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of
data from 170,000 partici- pants in 26 randomised trials. Lancet. 2010;376:1670– 1681.

42. SUBCLINICAL ATHEROSCLEROSIS AND RISK
ASSESSMENT
• Definition:-
1. Significant atherosclerotic plaque in an asymptomatic patient on CTCA/
Coronary artery calcification
2. Carotid plaque on USG or Angiography
3. Abnormal ABI or plaque noted on Peripheral arterial angiography
• To be started on High intensity Statin therapy
Rozanski, Alan, et al. "Impact of coronary artery calcium scanning on coronary risk factors and
downstream testing: the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging
Research) prospective randomized trial." Journal of the American College of Cardiology 57.15 (2011):
1622-1632.

43. • CAC > 1000 AU:- very high annual clinical ASCVD risk(3.3 events per 100 person
years)
• Society of Cardiothoracic Computed Tomography and Society of Thoracic
Radiology guidelines:- COR I for at-least qualitative interpretation of
CAC(mild/moderate/severe or heavy) on all Chest CTs
• Presence of Moderate calcium correlated with CAC of > 100 AU
Peng AW, Mirbolouk M, Orimoloye OA, et al. Long-term all-cause and cause-specific mortality in asymptomatic patients with
CAC >1,000: results from the CAC consortium. J Am Coll CardiolImg. 2020;13:83–93.
Peng AW, Dardari ZA, Blumenthal RS, et al. Very high coronary artery calcium (> 1000) and association with cardiovascular
disease events, non-cardiovascular disease outcomes, and mortality: results from MESA. Circulation. 2021;143:1571–1583.

44. SPECIAL POPULATIONS
• HFrEF:-
1. CORONA and GISSI-HF trials:- No significant benefit of Rosuvastatin 10 mg,
2. AHA/ACC(2018):- Reasonable to use Statins in HFrEF(ICMP), if life expectancy of
3-5 years
3. IMPROVE-IT:- Addition of Ezetimibe may be reasonable
4. Alirocumab:- failed to show benefit + increased non fatal MI
Feinstein, Matthew J., et al. "Do statins reduce the risk of myocardial infarction in patients with heart failure? A pooled individual‐level
reanalysis of CORONA and GISSI‐HF." European Journal of Heart Failure 17.4 (2015): 434-441.
Cannon, Christopher P., et al. "Ezetimibe added to statin therapy after acute coronary syndromes." New England Journal of Medicine
372.25 (2015): 2387-2397.
Rosenson, Robert S., et al. "Evinacumab in patients with refractory hypercholesterolemia." New England Journal of Medicine 383.24
(2020): 2307-2319.

45. • MHD:-
1. AHA/ACC(2018):- CKD not on MHD:- Statin +/- Ezetimibe
2. SHARP Trial, AURORA Trial, 4D trial:- No benefit of statins in MHD patients
3. ODYSSEY and FOURIER trials:- MHD patients excluded
Baigent, Colin, et al. "The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart
and Renal Protection): a randomised placebo-controlled trial." The Lancet 377.9784 (2011): 2181-2192.
Fellström, Bengt C., et al. "Rosuvastatin and cardiovascular events in patients undergoing hemodialysis." New England Journal of Medicine 360.14
(2009): 1395-1407.
Wanner, Christoph, et al. "Randomized controlled trial on the efficacy and safety of atorvastatin in patients with type 2 diabetes on hemodialysis
(4D study): demographic and baseline characteristics." Kidney and Blood Pressure Research 27.4 (2004): 259-266.
Sabatine, Marc S., et al. "Evolocumab and clinical outcomes in patients with cardiovascular disease." New England Journal of Medicine 376.18
(2017): 1713-1722.
Schwartz, Gregory G., et al. "Alirocumab and cardiovascular outcomes after acute coronary syndrome." New England Journal of Medicine 379.22
(2018): 2097-2107.

46. LAI GUIDELINES

47. INTRODUCTION
• India is in the middle of an ASCVD epidemic
• CAD manifests almost a decade earlier in India than in western countries
• Incidence of CAD is increasing most rapidly amongst patients younger than 40 years
of age
Prabhakaran D, Jeemon P, Roy A. Cardiovascular diseases in India: Current epidemiology and future directions. Circulation 2016;
133:1605-20.
Duell, P. Barton, et al. "The epidemic of atherosclerotic cardiovascular disease in India." Journal of clinical lipidology 14.2 (2020):
170-172. Kalra, Dinesh K., et al. "JCL roundtable: South Asian atherosclerotic risk." Journal of Clinical Lipidology 14.2 (2020): 161-
169.
Kalra, Dinesh K., et al. "JCL roundtable: South Asian atherosclerotic risk." Journal of Clinical Lipidology 14.2 (2020): 161-169.

48. ICMR-INDIAB STUDY

50. LIFESTYLE MODIFICATION
• DIET:-
1. LAI recommends the adoption of a Mediterranean dietary pattern
2. Vegetables, fruits, whole grains, low fat dairy products, poultry, fish, legumes
3. Combination of oils rich in PUFA and MUFA
4. Limiting intake of sweets, sugar, sweetened beverages and meat
• PHYSICAL ACTIVITY:-
1. 150 min/week of Moderate intensity, or 75 min/week of vigorous intensity aerobic
physical activity, or an equivalent combination of both, Spread throughout the week
2. Muscle strengthening exercise at-least 2 days per week
De Lorgeril, Michel, et al. "Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial
infarction: final report of the Lyon Diet Heart Study." Circulation 99.6 (1999): 779-785.

51. • ALCOHOL INTAKE:-
1. Should preferably be avoided by Indians
2. Up-to 1 drink for females and 2 for males
• TOBACCO:-
1. Complete abstinence from all tobacco containing products
• STRESS MANAGEMENT and adequate sleep
Di Castelnuovo, Augusto, et al. "Alcohol dosing and total mortality in men and women: an updated meta-analysis of 34 prospective
studies." Archives of internal medicine 166.22 (2006): 2437-2445.
Neetu Chandra Sharma. Alcohol consumption in India doubled in 11 years: WHO report. 2018.
Prasad, Barre Vijaya, Shamsi Akbar, and R. Ashwini. "Cardiovascular disease in elderly an early care: biopsychosocial perspective."
Handbook of Research on Geriatric Health, Treatment, and Care. IGI Global, 2018. 175-193.

52. RISK STRATIFICATION-LAI 2020

53. • 5 categories are recommended: low risk, moderate risk, high risk, very high risk and extremely high-risk
groups;
• Non-HDL-C as co-primary target because of increased prevalence of atherogenic dyslipidemia in India
• In absence of our own risk score calculator, only risk factors are used for risk assessment

56. • Statin + Ezetimibe combination is recommended to achieve LDL cholesterol target early
after acute coronary events
• It is recommended to add another non-statin drug if LDL-C target of <55 mg/dl is not
achieved at 4 weeks: choices are bempedoic acid, PCSK9i or inclisiran

57. TRIGLYCERIDES AND ASCVD
• Data from Randomized trials have shown that individuals with Mixed
hyperlipidemia (Elevated TGs, Elevated LDL, Decreased HDL) have the highest risk
of CV events:- Helsinki Heart Study and bezafibrate Infarction program
• PROVE-IT TIMI 22 study:- Elevated TGs, 150 mg/dl or more, increased the risk of
MI/ mortality, despite patients having achieved LDL-C < 70 mg/dl
• 22 year follow up of Bezafibrate Infarction Program study, concluded that in
patients with established CHD, higher TG levels are associated with increased
mortality
Tenenbaum, Alexander, et al. "Bezafibrate for the secondary prevention of myocardial infarction in patients with metabolic syndrome." Archives of
internal medicine 165.10 (2005): 1154-1160.
Ray, Kausik K., et al. "Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-
TIMI 22 trial." Journal of the American College of Cardiology 46.8 (2005): 1405-1410.

58. • Classification of Fasting TG levels:-
1. < 100 mg/dl- Optimal
2. < 150 mg/dl- Normal
3. 150-199 mg/dl- Borderline High
4. 200-499 mg/dl- High
5. 500 mg/dl- Very High
• Fasting v/s Non fasting TG levels:-
• In most patients, there is a clinically un-important increase in TG
concentration by 18-36 mg/dl, 2-6 hours after meals.
• Indians have Atherogenic dyslipidemia:- High TG + High LDL-C + Low HDL-C

59. • Copenhagen City Heart study and Copenhagen population Study:-
Non fasting TG levels may be more significant predictors of CVD risk than fasting.
• LAI recommends both Fasting and Non fasting lipid profile in Indian subjects with
Dyslipidemia
1. Fasting:- for LDL-C levels
2. Non fasting:- for Post prandial Hypertriglyceridemia
• Pharmacologic agents:-
1. Fibrates:- 30-50% TG reduction
2. Niacin:- 20-5-% TG reduction
3. Omega3 fatty acid:- 20-5-% TG reduction
4. Statins:- 10-30 % TG reduction
5. Ezetimibe:- 5-10% TG reduction

61. COMPARISON OF GUIDELINES

62. ESC/ESA AHA/ACC LAI
RISK ESTIMATION TOOLS SCORE-2
(Systematic COronary Risk
Evaluation)
ASCVD
(Arteriosclerotic
Cardiovascular Disease Risk
Estimator)
RISK
STRATIFICATION/FACTORS
RISK CATEGORIES 10-year SCORE2/SCORE2-OP
percentages (fatal and non-
fatal CVD risk)
<50 years: <2.5%, 2.5–7.5%,
≥7.5%
50–69 years: <5%, 5–10%,
≥10%
≥70 years: <7.5%, 7.5–15%,
≥15%
(Low-to-moderate-risk, high-
risk and very high-risk,
respectively
10-year risk ASCVD
percentages (fatal and non-
fatal ASCVD)
High: ≥20%
Intermediate: ≥7.5–<20%
Borderline: 5–<7.5%
Low: <5%
5 categories :
• low risk,
• moderate risk,
• high risk,
• very high risk and
• extremely high-risk
groups;
based on risk factors only
and not based on any risk
calculator

63. ESC/ESA AHA/ACC LAI
Risk-modifying and
enhancing factors
Risk Modifiers-
Family history of premature
CVD (men: <55 years and
women: <60 years)
Risk-Enhancing Factors-
Family history of premature
ASCVD (males: <55 years;
females: <65 years)
Obesity and central obesity ABI < 0.9
Physical inactivity
Social deprivation and
psychosocial stress, including
vital exhaustion
High-risk race/ethnicities
(e.g., South Asian ancestry)

64. ESC/ESA AHA/ACC LAI
Biomarkers
1. Elevated high-sensitivity
C-reactive protein (≥2.0
mg/L)
Elevated Lp(a): A relative
indication for its
measurement is family
history of premature ASCVD.
2. An Lp(a) ≥ 50 mg/dL or
≥125 nmol/L constitutes a
risk-enhancing factor,
especially at higher levels of
Lp(a)
3. Elevated ApoB ≥ 130
mg/dL: A relative indication
for its measurement would
be triglyceride ≥200 mg/dL.
A level ≥ 130 mg/dL
corresponds to an LDL-C ≥
160 mg/dL and constitutes a
risk-enhancing factor.

65. TREATMENT GOALS ESC/ESA AHA/ACC LAI
PRIMARY PREVENTION Despite maximally tolerated
statin dosage,
≥50% LDL-C reduction from
baseline and LDL-C goal of
(55 mg/dL) in very high-risk
groups,
(<70 mg/dL) in high-risk
groups,
(<100 mg/dL) in moderate-
risk groups
(<116 mg/dL) in low-risk
groups
is not achieved, treatment
intensification with non-
statin agents is
recommended.
In adults without ASCVD or
diabetes with
LDL-C level of 70–189 mg/dL,
if patient has ≥20% risk, and
In adults with diabetes
without ASCVD and with LDL-
C < 190 mg/dL,
if ≥50% reduction in LDL-C
level or LDL-C < 70 mg/dL or
non-HDL-C < 100 mg/dL are
not achieved, despite statin
therapy, ezetimibe additon
may be reasonable.
In adults without ASCVD and
LDL-C ≥ 190 mg/dL,
if ≥50% reduction in LDL-C
level or LDL-C < 100 mg/dL or
non-HDL-C < 130 mg/dL are
not achieved, despite statin
therapy, non-statin agents
are recommended.

66. ESC/ESA AHA/ACC LAI
SECONDARY PREVENTION If LDL-C ≥ 55 mg/dL, despite
maximally tolerated statin
dosage, addition of
ezetimibe or PCSK9
inhibitors after ezetimibe
initiation is recommended.
Patients with ASCVD and at
very high-risk adults with
ASCVD at very high-risk, if
≥50% reduction of LDL-C
level or LDL-C < 55 mg/dL
are not achieved despite
statin therapy, non-statin
agents are recommended.
For patients with ASCVD but
without very high- risk, if
≥50% reduction of LDL-C
level or LDL-C < 70 mg/dL
are not achieved despite
statin therapy non-statin
agents are recommended

67. ESC/ESA AHA/ACC LAI
Definitions of very high-risk
patients
To have one of these
conditions below
Two or more major ASCVD
events OR
One major event and >1 high-
risk condition
• Documented clinical ASCVD
• Type 2 diabetes mellitus
with target organ damage or
at least three major risk
factors, or early onset
T1DM of long duration (>20y)
• Severe CKD (eGFR < 30
mL/min per 1.73 m2).
• A calculated SCORE ≥ 10%
or 10-year risk of fatal CVD
• FH with ASCVD or with
another major risk factor
Major ASCVD events
• Recent ACS (within the past
12 months)
• History of MI (other than
the recent ACS event listed
above)
• History of ischemic stroke
• Symptomatic peripheral
arterial disease (history of
claudication with ABI
<0.85, or previous
revascularization or
amputation)
Very high-risk category has
individuals with clinical
evidence of atherosclerotic
CAD, atherosclerotic disease
in other vascular beds,
diabetes >20 years, HeFH
with ASCVD, or coronary
imaging showing >50 % lesion
in 2 coronary vessels. ASCVD
includes coronary artery,
cerebrovascular and
peripheral vascular disease

68. ESC/ESA AHA/ACC LAI
High-risk conditions
• Age ≥ 65 years
• Diabetes mellitus
• Hypertension
• CKD (eGFR 15–59 mL/min
per 1.73 m2)
• History of CHF
• Current smoking
• Heterozygous FH
• History of prior CABG or
PCI outside of the major
ASCVD event(s)
• Persistently elevated LDL-C
≥ 100 mg/dL, despite
maximally
tolerated statin therapy and
ezetimibe
Extremely high-risk group
comprises those with
recurrent vascular events
and ASCVD with genetic
dyslipidemias (FH & High
Lp(a)).

69. ESC/ESA AHA/ACC LAI
LIPID MEASUREMENT Non-fasting lipid profile fasting lipid profile BOTH
Lp(a) MEASUREMENTS with a family H/o premature
ASCVD or a personal H/o
premature ASCVD and
consider Lp(a) as a risk
enhancing factor
once in each individual’s
lifetime, especially
recommended if family H/o
premature ASCVD
I/v/o high prevalence of
raised Lp(a) in Indian
population, it’s routine
assessment will help in
detecting high risk
individuals(Lp(a)> 50 mg/dl)

70. CONCLUSION
• A Healthy lifestyle should be emphasized across the course of life.
• All guidelines strongly advocate that LDL-C should be our primary target and the
intensity of treatment should increase as the risk of the patient increases.
• Throughout the range of LDL-C, Lower is Better, with no lower threshold and
also earlier reduction of LDL-C is better.

71. • ApoB may be a better measure of exposure to pro-atherogenic
lipoproteins, helpful when LDL-C underestimates this burden:- High TG,
DM, very low LDL.
• Lp(a) levels may help identify the inherited risk of ASCVD.
• Non-HDL-C is an accurate predictor of CV risk, particularly for those on
Statin therapy.
• There are no known adverse effects of very low LDL-C levels.

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73. THANK YOU