Management of dyslipidemia

Approach & management of of lipid disorders

1. Evaluation and Management
of Dyslipidemia
Mohsen Eledrisi, MD, FACE, FACP
Department of Medicine
Hamad Medical Corporation
Doha, Qatar
[email protected]
ميحرلا نمحرلا الله مسب

2. DYSLIPIDEMIA
-A consequence of abnormal lipoprotein metabolism
-It includes:
–High total cholesterol
–High low-density lipoproteins (LDL)
–High triglycerides (TG)
–Low high-density lipoproteins (HDL)

3. Primary dyslipidemia
•Single or multiple gene mutation resulting in disturbance of
LDL, HDL or/and trigylcerides production or clearance
•Suspect in patients with :
–Premature Heart Disease
–Family history of atherosclerotic disease
–T. cholesterol Level > 6.2 mmol (240 mg)
–Physical signs of dyslipidemia (xanthoma, xanthelasma)

4. Physical exam
Xanthoma

5. Physical exam
Xanthelasma Arcus senilis

6. High cholesterol is associated
with coronary heart disease
0
25
50
75
100
125
150
204205-234235-264265-294 295
Castelli W. Am J Med 1984;76:4
CHD Incidence
per 1000
Total cholesterol (mg/dL)
The Framingham Heart Study

7. Secondary dyslipidemia
1) LDL:
-Obesity, hypothyroidism, obstructive liver disease,
nephrotic syndrome, corticosteroids, diuretics,
cyclosporine, amiodarone
2) TG:
-Obesity, hypothyroidism, diabetes, nephrotic syndrome,
CKD, corticosteroids, oral estrogens, anabolic steroids,
Beta-blockers, thiazides, alcohol, antiretroviral therapy

8. •National Cholesterol Education Program's Adult
Treatment Panel III (ATP III)
•Start at age 20
•Every 5 years
•Fasting (total cholesterol, LDL-C, HDL-C, and TG)
•Endorsed by American Heart Association
Screening for dyslipidemia:
ATP III guidelines
ATP III. JAMA2001;285:2486-2497

9. •Men age ≥ 35
•Women age ≥ 45
•Men 20-35 & Women 20-45 if any CHD risk factors:
–Prior CHD or abdominal aortic aneurysm, peripheral artery
disease, carotid artery stenosis
–DM
–HTN
–Smoking
–A family history of cardiovascular disease
–Obesity
Screening for dyslipidemia
(United States Preventive
Services Task Force
recommendations)
www.uspreventiveservicestaskforce.org

10. Case 1
•A 58-year-old man follows for hypertension
•No diabetes, Non-smoker
•He had a minor stroke 3 years ago
•Total cholesterol 4.7 mmol (182 mg)
•LDL 2.4 mmol (92 mg)
•HDL 1 mmol (38 mg)
•How to manage his lipids?

11. American Heart Association/American
College of Cardiology Guidelines
• Statins are recommended for 4 groups:
1) Clinical ASCVD
2) LDL-C ≥ 4.9 mmol (190 mg)
3) Age 40-75 years with diabetes
4) Age 40-75 years with ASCVD risk ≥ 20%
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

12. Our approach
• Start by:
1) Does my patient have ASCVD?
Yes
Start Statin

13. ASCVD
(Atherosclerotic
cardiovascular disease)
•History of myocardial infarction
•Acute coronary syndromes
•Stable or unstable angina
•Coronary or other arterial revascularization
•Stroke or TIA
•Peripheral arterial disease

14. Patients with ASCVD
•No need for ASCVD risk assessment
•They need statins regardless of other risk
factors or age
•Those are classified into:
1) Very high risk
2) Stable ASCVD

15. Very high risk ASCVD
•Major ASCVD events:
–Acute coronary syndrome within 1 year, Myocardial
infarction, ischemic stroke, symptomatic PAD
•High risk conditions:
–Age ≥ 65, CABG, PCI, DM, HTN, CKD, smoking,
familial hypercholesterolemia, LDL ≥ 2.6 mmol (100 mg)
on Statin & Ezetimibe
Very high risk is defined as:
–2 or more major events or 1 major + 2 or more high
risk conditions
If none = stable ASCVD

16. Statins for stable
ASCVD
Age ≤ 75 years: High-intensity statin
Age > 75 years:
-Moderate intensity statin if starting treatment
-If already on high-intensity statin: continue
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

17. Statins for very
high risk ASCVD
High-intensity statin
or maximal tolerated statin

18. High-intensity statins
•Lower LDL by ≥50 %
–Atorvastatin 40 or 80 mg qd
–Rosuvastatin 20 or 40 mg qd

19. Moderate-intensity statins
•Lower LDL by 30 to 49 %:
–Atorvastatin 10 or 20 mg qd
–Fluvastatin XL 80 mg qd
–Lovastatin 40 or 80 mg qdd
–Pitavastatin 1, 2, 4 mg qd
–Pravastatin 40 or 80 mg qd
–Rosuvastatin 5 or 10 mg qd
–Simvastatin 20 or 40 mg qd

20. Low-intensity statins
•Only used if patients could not tolerate moderate
intensity statin
•Lower LDL by < 30 %:
–Fluvastatin 20 or 40 mg qd
–Lovastatin 20 qd
–Pravastatin 10 or 20 mg qd
–Simvastatin 10 mg qd

21. Labs before
starting statins
•Obtain ALT
•No need to monitor liver enzymes after starting statins
unless symptoms of hepatic dysfunction develop
(abdominal pain, vomiting, jaundice, fatigue, dark urine,
yellow sclera) or the patient is on other medications that
may affect liver function
ACC/AHA Guidelines. Circulation 2014;129 (Suppl 2).
www.fda.gov

22. Labs before starting
statins
Serum creatinine kinase (CK):
•ACC/AHA: recommend baseline serum creatinine kinase
in high risk patients [expert opinion]:
–A personal or family history of statin intolerance or
–Clinical presentation or
–Muscle disease or
–On drugs that might increase the risk of myopathy
•Periodic monitoring is not recommended
ACC/AHA Guidelines. Circulation 2014;129 (Suppl 2):S1

23. F/U after starting statin
•Lipids after 1-3 months
•Then every 3-12 months as needed
•To assess response & adherence
•High-intensity statins:
–LDL by ≥ 50 %
•Moderate-intensity statins:
–LDL by 30-50 %
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

24. Case 2
•A 54-year-old man with DM 2 & HTN
•He had CAD (acute MI with stent) 3 years ago
•Atorvastatin 40 mg qd, insulin, ACEi, BB, ASA
•T. cholesterol 5.1 mmol (198 mg)
•LDL 3.1 mmol (120 mg)
•HDL 1 mmol (38 mg)
-What is your advice regarding lipid treatment?

25. High LDL despite statin
•Target LDL :
< 1.8 mmol (70 mg) if ASCVD
< 2.6 mmol (100 mg) if severe primary hypercholesterolemia
(baseline ≥ 4.9 mmol [190 mg])
•Assess adherence
•Assess response to statin (LDL before & after)
•Anecdotal reports about different response to
different statins
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

26. When to add
non-statin therapy?
•Ezetimibe:
1) ASCVD on maximal tolerated statin
with LDL ≥ 1.8 mmol(70 mg)
2) Severe primary hypercholesterolemia
(baseline LDL ≥ 4.9 mmol [190 mg]) on maximal
tolerated statin with LDL ≥ 2.6 mmol (100 mg)
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

27. Indications for
PCSK-9 inhibitors
1) Very high risk ASCVD on maximal tolerated
statin & Ezetimibe with LDL ≥ 1.8 mmol (70 mg)
2) Severe primary hypercholesterolemia (baseline
LDL ≥ 4.9 mmol [190 mg]) on maximal tolerated
statin & Ezetimibe with LDL ≥ 2.6 mmol (100 mg)
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

28. Case 3
•A 52-year-old man had a health check up
•No diabetes, No hypertension
•Non-smoker
•Total cholesterol: 8.0 mmol (310 mg)
•LDL 6.2 mmol (240 mg)
•HDL 1.1 mmol (40 mg)
•How to manage his lipids?

29. Our approach
• Start by:
1) Does my patient have ASCVD?
-if yes, start statin
-if no, go to question 2
2) What is the LDL level?

30. Severe primary
hypercholesterolemia
-For adult patients with:
LDL-C ≥ 4.9 mmol (190 mg)
-No need for ASCVD risk assessment
-They need statins regardless of risk or age
-High intensity statin
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003

31. •For all patients regardless of risk factors:
•DASH-like diet:
–Rich in fruits, vegetables, low fat diary products
–Reduce saturated and total fat
•Physical activity
•Weight control
•Smoking cessation
Lifestyle changes
ACC/AHA Guidelines. Circulation 2014;129 (Suppl 2).

32. •Modified diet and weight loss
•Upto 10-20 % in LDL levels in some patients
•Overall average 2-6 % 
How effective are
lifestyle changes?
Jenkins D et al. JAMA. 2011;306:831

33. CASE 4
•A 60-year-old man with diabetes and hypertension
•No smoking
•B.P.124/60
•T. cholesterol: 5.0 mmol (192 mg)
•LDL 2.4 mmol (92 mg)
•HDL 1 mmol (38 mg)
•How to manage lipids?

34. Case 4: approach
1) No ASCVD
2) LDL is < 4.9 mmol (190 mg)
Next question:
3) Does the patient have DM and age ≥ 40 years?
-If yes, start statin

35. Guidelines on lipids in DM
•There are 2 guidelines for patients with DM:
–American College of Cardiology/American Heart
Association (ACC/AHA)
–American Diabetes Association (ADA)
1) They differ in age criteria to prescribe statins
–ACC/AHA recommends statins for age 40-75 years
–ADA recommends statins for all patients age ≥40 years

36. Guidelines on lipids in DM
2) They also differ on how to decide on type of statins:
–ACC/AHA recommends assessing risk factors :
•Generally use moderate intensity statins
•High intensity statin if age 50-75 or multiple risk factors
–ADA recommends calculating 10-year ASCVD risk:
•Generally use moderate intensity statin
•Use high intensity if ASCVD risk > 20 % or multiple risk
factors

37. Statins in diabetes:
ADAguidelines
Age ≥ 40 years
Moderate
intensity statin
American Diabetes Association. Diabetes Care 2019;42(Suppl.1):S103.
High intensity statin
•If multiple CV risk factors
or
•10-year ASCVD risk > 20 %
•CV risk factors:
( LDL ≥ 2.6 mmol, HTN, CKD,
albuminuria, smoking, F/H of
premature ASCVD)

38. Statins in diabetes:
ACC/AHAguidelines
Age 40-75 years
Moderate
intensity statin
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003
High intensity statin
•If age 50-75 years
or
•Multiple CV risk factors

39. How about DM age < 40 or > 75?
•Here guidelines are different
•ACC/AHA:
–Assess other risk factors:
–Consider Statin if:
•LDL ≥ 4.1 mmol (160 mg)
•Family history of premature ASCVD
•Elevated high sensitive CRP level
•Low ankle brachial index
•High coronary artery calcium on CT-scan

40. ADA 2019 guidelines
•Age < 40:
•Any CVD risk*: consider moderate-intensity statin
•Multiple risk factors: consider high-intensity statin
•Age > 75:
•Moderate-intensity statin
•Multiple risk factors: consider high-intensity statin
* CVD risk factors: LDL 2.6 mmol (100 mg), hypertension, smoking,
CKD, albuminuria, or family h/o premature CVD

41. Case 5
•A 58-year-old man no DM, no HTN
•No smoking
•BMI 31, B.P. 124/72
•T. cholesterol 5.2 mmol (200 mg)
•LDL 3.2 mmol (123 mg)
•HDL 0.8 mmol (31 mg)
•Lab reference range indicates “desirable LDL < 3.3
mmol (130 mg)”
•How would you approach?

42. Case 5: approach
1) No ASCVD
2) LDL is < 4.9 mmol (190 mg)
3) No DM with age ≥ 40 years
Next step:
4) Is age 40-75 years?
-If yes, do 10-year ASCVD risk calculation

47. 10-year ASCVD risk calculator
7.5-19.9 %
(Intermediate risk)
Evaluate
risk enhancers
AHA/ACC Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003
High intensity
statin
LDL ≥ 4.1 mmol, CKD,metabolic
syndrome, F/H of premature ASCVD,
chronic inflammation (psoriasis, RA, HIV),
premature menopause, prior preeclampsia,
or persistent ↑ TG (≥ 1.97 mmol [175 mg])
≥ 20 %
(High risk)
5-7.4 %
(borderline risk)
Moderate intensity
statin

48. Definitions
•Family history of premature CVD:
–Male age < 55 or female age < 65
•Metabolic syndrome:
–Increased waist circumference (men > 102 cm;
women > 88 cm), elevated TG (>1.97 mmol [175
mg], elevated BP, elevated glucose, low HDL
–Any 3 of the above constitute metabolic syndrome

49. Other risk enhancers
•Those are not routinely done
•The presence of any favors the decision for statin
-High-sensitivity C-reactive protein (≥ 2.0 mg/L)
-Elevated lipoprotein (a) [ ≥ 50 mg/dL or ≥125 nmol/L]
-Elevated apo B [≥130 mg/dL]
-Low ankle brachial index [<0.9]

50. When to do CT coronary?
ASCVD risk
7.5-19.9 %
ACC/AHA Guidelines. J Am Coll Cardiol 2018 10.1016/j.jacc.2018.11.003
Consider CT angio to measure
coronary artery calcium
(CAC score)
Patient concerned
or reluctant
to take statin
1-99
Statin
favored
≥ 100
Statin
recommended

51. Case 5: plan
-Do 10-year ASCVD risk calculation
-Risk = 10.8 %
-Need to assess for risk enhancers
-If any: offer moderate intensity statin
-If none: advise lifestyle changes

52. Case 5
•A 34-year-old healthy lady
•No family history of ASCVD
•T. cholesterol: 5.5 mmol(212 mg)
•LDL 3.6 mmol (140 mg)
•HDL 1.3 mmol (52 mg)
•She is concerned about her LDL level since
lab. reference range indicates “desirable < 3.3
mmol (130 mg)”
-What is your advice?

53. Case 5: approach
1) No ASCVD
2) LDL is < 4.9 mmol (190 mg)
3) No Diabetes with age ≥ 40 years
4) Is age 40-75 years?
-If no, this is not in the high risk groups

54. Not in the statin groups
•Age 20-39 year (risk calculation is not studied)
-Advise lifestyle changes
-Consider statin if:
-LDL ≥ 4.1 mmol (160 mg)
OR
-Family history of premature ASCVD

55. Case 5: approach
-The lady is < 40 years of age
-Risk calculation has not be validated for this age
-We need to look at other risk factors
-She has no family history of ASCVD
-Her LDL is not ≥ 4.1 mmol (160 mg)
-So, no treatment is recommended
-Advise lifestyle changes

56. CASE 6
•A 55-year-old woman with diabetes and hypertension
•Statin is advised
•Before treatment:
–ALT 72 (normal < 40)
–AST 55 (normal < 40)
•How to approach?

57. CASE 6: approach
•Patient with abnormal baseline ALT
•Evaluation for liver disease before staring statin:
–Medication history
–Hepatitis B virus
–Hepatitis C virus
–Liver ultrasound
•Many patients will have fatty liver

58. Starting statin with
high ALT
•Monitor ALT
•Education:
•Importance of follow up
•Symptoms (abdominal pain, vomiting, jaundice)
•If so, stop statin and early follow up

59. CASE 6: follow up
•Hepatitis B and Hepatitis C virus serology: negative
•Liver ultrasound: fatty liver
•Rosuvastatin 20 mg qdstarted
•After 3 months
–ALT 130 (was 72)
–AST 85 (was 45)
•What is the plan?

60. Statin-induced liver injury
•Increased ALT after staring statin
•Rare (< 1 %)
•If ALT < 3 times upper limit of normal:
•Continue statin
•Monitor ALT
•Educate the patient:
-Symptoms (abdominal pain, vomiting, jaundice)
-If so, stop statin & follow up

61. Statin-induced liver injury
•If ALT > 3 times upper limit of normal or symptoms:
•Stop statin. Monitor ALT/AST
•When ALT returns to baseline:
-Can challenge with another statin (Pravastatin
appears to be the safest)
-Avoid the same statin

62. Can Statins be used in
chronic liver disease?
•Yes, if liver disease is stable
•Can be used in compensated cirrhosis
•Extreme precaution in decompensated cirrhosis
•Monitor ALT:
•Before starting statin
•When increasing dose
•And periodically
Moctezuma-Velázquez , et al. CCurr Treat Options Gastroenterol.2018;16:226

63. CASE 7
•A 55-year-old woman with type 2 DM & HTN
•LDL 3.3 mmol (140 mg)
•Atorvastatin 40 mg started
•On follow up, she reports muscle pain
•How to manage?

64. Statin-related myopathy
•History:
•Onset of muscle symptoms
•Severity of symptoms (mild, tolerable, frequency..)
•Relation to activity
•On other medications?
•Physical exam

65. Statin-related adverse
muscle events
•Starts weeks to months after starting statin
•Degrees:
1) Myalgia (muscle aches, soreness, stiffness, tenderness, cramps)
2) Myopathy(muscle weakness, with or without in serum CK)
3) Myositis(muscle inflammation)
4) Myonecrosis(in serum CK)
5) Rhabdomyolysis(myonecrosiswith myoglobinuriaor acute
kidney injury)
National Lipid Association. J Clin Lipidol 2014;8(3 Suppl):S58.

66. Risk factors for
statin-related myopathy
•High-intensity statin
•Advanced age (> 65 years)
•Female gender
•Vitamin D deficiency
•Hypothyroidism
•Alcohol
•Kidney or liver disease
•Major surgery
•Medications:
•Fibrates, Diltiazem, Verapamil, Macrolides, Amiodarone,
Antifungals, Cyclosporine
Joy T, HegeleR. Ann Intern Med 2009;150:858

67. Management of Statin-related
adverse muscle events
•If patient cannot tolerate: stop statin
•Wait for symptoms to resolve. Check CK
•Assess for:
•Drug interaction
•Vitamin D deficiency
•Hypothyroidism
•If any of above:
•Drugs: Fluva, Prava, Rosuvastatinhave less interaction
•Others: correct then resume same statin

68. Management of moderate to
severe symptoms
•Stop statin
•Assess risk factors
•Check serum CK
•Severe symptoms:
•Consider rhabdomyolysis
•Serum creatinine, urine myoglobin
•May need hospital admission

69. Recurrence of
Statin-related adverse
muscle events
•Switch to another statin
•Lowest risk : Fluvastatin
•Also Pravastatin has low risk
•May try low dose rosuvastatin (5 or 10 mg qd)
•If symptoms recur:
•Use less frequent dosing (of above)
–every other day or (Once, twice, 3 times/week)
•If still symptoms, stop statin
-Use non-statin agents (Ezetimibe)
Joy T, Hegele R. Ann Intern Med 2009;150:858

70. Statin-related adverse muscle event
Stop statin.Wait for symptoms to resolve
Drug interaction with statin
Assess for hypothyroidism
& vitamin D deficiency
No
Present
Yes
Recurrence of symptoms
Modify medications if possible
Or use Prava, Fluva, or Rosuvastatin
Absent
Correct then
resume statin
Recurrence of symptoms
Taking
Prava or Fluvastatin?
Yes
No
Alternate day
dose
Stop statin
Recurrence of
symptoms
Use
Prava or Fluvastatin

71. Safety issues with statins
•Increased risk of diabetes
•Risk is increased by about 9 %
•Higher risk with high-intensity statins
•Risk in patients at risk for DM (prediabetes, family
history, physical inactivity)
•Lowest risk: Lovastatin & Fluvastatin then Pravastatin
•Benefits outweigh risks particularly in high risk patients
•Encourage healthy lifestyle & monitor glucose
ACC/AHA Guidelines. Circulation 2014;129 (Suppl 2).
Carter A, et al. BMJ2013;346:f2610; Sattar N, et al. 2010 Lancet 2010; 375: 735.

72. Statins safety recommendations
•Is very low LDL harmful?
–ACC/AHA suggests to lower the dose of statin if LDL
level on 2 consecutive occasions is < 1.0 mmol(40 mg)
–This is given “Evidence level C” = weak recommendation
–This approach was undertaken in clinical trials
–However, no evidence till date has shown that low LDL is
harmful
ACC/AHA Guidelines. Circulation 2014;129 (Suppl 2).

73. CASE 8
•A 38-year-old woman with DM 2
•Metformin, Sitagliptin, oral contraceptive pill
•BMI 34, normal B.P.
•LDL: “cannot be determined “
•TG 11.1 mmol(1010 mg)
•HDL 0.6 mmol(25 mg)
•How to approach?

74. Serum triglycerides
ATP III guidelines.
•< 1.7 mmol (150 mg): Normal
•1.7-2.25 mmol (150-199 mg): Borderline high
•2.26-5.6 mmol (200-499 mg): High
•5.6 mmol (500 mg): Very high

75. Approach to high TG
•Possible association of high TG with CVD
•Borderline high & High: [1.7-5.6 (150-499 mg)]
•Life-style changes
•No strong evidence that treatment has benefit
•Weak evidence suggest to treat patients with DM who also
have low HDL

76. Very high TG: assess for
secondary causes
•Uncontrolled DM
•Alcohol
•Chronic Kidney disease
•Nephrotic syndrome
•Liver disease
•Hypothyroidism
•Drugs (estrogens, steroids, -Blockers, antipsychotics,
tamoxifen, immunosuppressants)

77. Back to our case 8
•TG 11.1 mmol(1010 mg)
•The patient has very high TG [5.7 mmol(500 mg)]
•Need to look for secondary causes:
–Her glucose is uncontrolled (A1c 11)
–She is on oral contraceptive pill
–Normal liver & kidney function
–No alcohol
–Thyroid function is normal

78. Case 8: PLAN
•Control glucose:
–Insulin is indicated (which will help TG)]
•Stop OCP:
–Change to another contraceptive method
•Advise diet and weight loss
•F/U lipids in 2-3 months
•If TG still very high:
–Consider medications

79. Treatment of very high TG
•Fibrates:
–Most effective; reduce TG by ≥ 50 %
1) Fenofibrate: comes in several forms:
•Nanocrystal formulation 145 mg daily taken without
regard to meals
•Micronized capsules 200 mg daily taken with dinner
•As fenofibricacid (also called choline fenofibrate);
145 mg daily without regard to meals)
2) Gemfibrozil 600 mg bid (combination with many
statins is not recommended due to risk of myopathy)

80. Treatment of very high TG
•Omega-3 fatty acids:
–Lowers TG by up to 45 %
–Can be used alone or combined with fibrates
–CanincreaseLDLcholesterol
–Dose: 1-2 grams bid
•Statins:
–Can lower TG by 20-40 %
–High intensitystatins are more effective

81. Low HDL-cholesterol
•< 1 mmol (40 mg) in men; < 1.3 mmol (50 mg) in women
•Low HDL is a risk factor for CAD
•Raising HDL levels did not lower the risk of CVD
•Physical activity, smoking cessation, weight loss
•Statin + Niacin is not recommended. May stroke
American Diabetes Association. Diabetes Care 2019;42(Suppl.1):S103.
HPS-2 THRIVE study. N EnglJ Med 2014;371:203; AIM-HIGH study. N EngJ Med 2011;365:2255
ACC/AHA Guideline. Circulation 2014;129 (Suppl 2)

82. Summary-1
•Statins for:
•ASCVD: (High-intensity statin)
•LDL 4.9 mmol (190 mg): (High-intensity statin)
•DM age 40 years:
•Generally use moderate-intensity statin
•High-intensity statin if multiple risk factors or
ASCVD risk > 20 %

83. Summary-2
•For non-DM, age 40-75:
•Do risk calculation:
•Risk 20 %: high-intensity statin
•Risk 7.5-19.9 %: look for risk enhancers:
-If any: moderate-intensity statin
•For age < 40:
•Risk calculation has not yet been validated
•Statin if
-LDL 4.1 mmol(160 mg) or family history of premature ASCVD