Key Points
- An elevated level of cholesterol carried by circulating apolipoprotein (apo) B–containing lipoproteins (non-high-density lipoprotein cholesterol [non-HDL-C] and low-density lipoprotein cholesterol [LDL-C], termed atherogenic cholesterol) is a root cause of atherosclerosis, the key process contributing to most clinical atherosclerotic cardiovascular disease (ASCVD) events.
- Reducing elevated levels of atherogenic cholesterol will lower ASCVD risk in proportion to the extent that atherogenic cholesterol is reduced. This benefit is presumed to result from atherogenic cholesterol lowering through multiple modalities, including lifestyle modification and drug therapies.
- The intensity of risk-reduction therapy should generally be adjusted to the patient’s absolute risk for an ASCVD event.
- Atherosclerosis is a process that often begins early in life and progresses for decades before resulting in a clinical ASCVD event. Therefore, both intermediate-term and long-term/lifetime risk should be considered when assessing the potential benefits and hazards of risk-reduction therapies.
- For patients in whom lipid-lowering drug therapy is indicated, statin treatment is the primary modality for reducing ASCVD risk.
- Non-lipid ASCVD risk factors should also be managed appropriately, particularly high blood pressure, cigarette smoking, and diabetes mellitus.
- In all adults (≥20 years of age), a fasting or nonfasting lipoprotein profile should be obtained at least every 5 years.
- At a minimum, this should include total cholesterol (total-C) and HDL-C, which allows calculation of non-HDL-C (total-C minus HDL-C). If fasting (generally 9-12 hours), the LDL-C level may be calculated, provided that the triglyceride concentration is <400 mg/dL. (See Table 7)
- For those with atherogenic cholesterol levels in the desirable range, public health recommendations regarding lifestyle should be emphasized.
Table 1. Criteria for Classification of ASCVD
- Myocardial infarction or other acute coronary syndrome
- Coronary or other revascularization procedure
- Transient ischemic attack
- Ischemic stroke
- Atherosclerotic peripheral arterial disease
- Includes ankle/brachial index <0.90
- Other documented atherosclerotic diseases such as:
- Coronary atherosclerosis
- Renal atherosclerosis
- Carotid plaque, ≥50% stenosis
- Aortic aneurysm secondary to atherosclerosis
Risk Assessment
- Risk category is used both for the purpose of defining treatment goals for atherogenic cholesterol (as well as apo B) and for defining the level of atherogenic cholesterol elevation at which pharmacotherapy to lower atherogenic cholesterol levels might be considered.
- As an option for those with 2 major ASCVD risk factors, the clinician may wish to perform quantitative risk scoring to estimate 10-year or long-term/lifetime risk for an ASCVD or coronary heart disease (CHD) event (See Table 3) and may also consider other risk indicators based on additional testing.
- It should be noted that the risk scoring thresholds are not intended to indicate “statin benefit groups.”
- It should be noted that the risk scoring thresholds are not intended to indicate “statin benefit groups.”
Table 2. Major Risk Factors for ASCVDa
|
|
|
|
|
a Levels of non-HDL-C and LDL-C are not listed, because these risk factors are used to assess risk category and treatment goals for atherogenic lipoprotein cholesterol levels. (See Table 4) Diabetes mellitus is not listed because it is considered a high or very high risk condition for ASCVD risk assessment purposes.
b CHD is defined as myocardial infarction (MI), coronary death, or a coronary revascularization procedure.
Table 3. Risk Calculators
High Risk Thresholda | |
---|---|
Adult Treatment Panel III Framingham
| ≥10% 10-year risk for a hard CHD event (MI or CHD death) |
Pooled Cohort Equations (American College of Cardiology/American Heart Association)
| ≥15% 10-year risk for a hard ASCVD event (MI, stroke or death from CHD or stroke) |
Framingham long-term (30-year to age 80)
| ≥45% risk for CVD (MI, CHD death or stroke) |
a These thresholds identify "high risk" individuals and are not intended to indicate "statin benefit" groups.
Table 4. Criteria for ASCVD Risk Assessment, Treatment Goals for Atherogenic Cholesterol, and Levels at Which to Consider Drug Therapy (mg/dL)
Table 5. High or Very High Risk Patient Groups
Quantitative risk scoring is not necessary for initial risk assessment in patients with the following conditionsa:
|
a Patients in these categories are all at high or very high risk for an ASCVD event and should be treated accordingly.
Table 6. Sequential Steps in ASCVD Risk Assessment
1. Identify patients with either very high risk or high risk conditions.a Very High Risk
High Risk
|
2. Count major ASCVD risk factors.
|
3. If 2 major ASCVD risk factors, risk scoring should be considered, and additional testing may be useful for some patients.
|
a Further risk assessment is not required after identifying the highest applicable risk level.
b End organ damage indicated by increased albumin/creatinine ratio (≥30 mg/g), CKD, or retinopathy.
c For patients with CKD stage 3B (GFR 30-44 mL/min/1.73 m2) or stage 4 (GFR 15-29 mL/min/1.73 m2) risk calculators should not be used because they may underestimate risk. Stage 5 CKD (or on hemodialysis) is a very high risk condition, but results from randomized, controlled trials of lipid-altering therapies have not provided convincing evidence of reduced numbers of ASCVD events in such patients. Therefore, no treatment goals for lipid therapy have been defined for stage 5 CKD.
d High risk threshold is defined as ≥10% using ATP III Framingham Risk Score for hard CHD (MI or CHD death), ≥15% using the 2013 Pooled Cohort Equations for hard ASCVD (MI, stroke or death from CHD or stroke), or ≥45% using the Framingham long-term (to age 80) CVD (MI, CHD death or stroke) risk calculation. Clinicians may prefer to use other risk calculators but should be aware that quantitative risk calculators vary in the clinical outcomes predicted (eg, CHD events, ASCVD events, cardiovascular mortality), the risk factors included in their calculation, and the time frame for their prediction (eg, 5 years, 10 years, or long-term or lifetime). Such calculators may omit certain risk indicators that can be very important in individual patients, provide only an approximate risk estimate, and require clinical judgment for interpretation.
Diagnosis
Table 7. Classifications of Cholesterol and Triglyceride Levels in mg/dL
Non-HDL-Ca | |
---|---|
<130 | Desirable |
130-159 | Above desirable |
160-189 | Borderline high |
190-219 | High |
≥220 | Very high |
LDL-C | |
<100 | Desirable |
100-129 | Above desirable |
130-159 | Borderline high |
160-189 | High |
≥190 | Very high |
HDL-C | |
<40 (men) | Low |
<50 (women) | Low |
Triglycerides | |
<150 | Normal |
150-199 | Borderline high |
200-499 | High |
≥500 | Very highb |
a Non-HDL-C = total-C minus HDL-C
b Severe hypertriglyceridemia is another term used for very high triglycerides in pharmaceutical product labeling.
Table 8. Drugs That May Elevate LDL-C or Triglyceride Concentrations
Drugs That Elevate LDL-C | Drugs That Elevate Triglycerides |
---|---|
|
|
Table 9. Risk Indicators (Other Than Major ASCVD Risk Factors) That Might be Considered for Risk Refinementa
- A severe disturbance in a major ASCVD risk factor, such as multi-pack per day smoking or strong family history of premature CHD
- Indicators of subclinical disease, including coronary artery calcium ≥300 Agatston unitsb is considered high risk
- LDL-C ≥160 mg/dL and/or non-HDL-C ≥190 mg/dL
- High-sensitivity C-reactive protein ≥2.0 mg/Lc
- Lipoprotein (a) ≥50 mg/dL (protein) using an isoform insensitive assay
- Urine albumin/creatinine ratio ≥30 mg/g
a The presence of one or more of the risk indicators listed may be considered, in conjunction with major ASCVD risk factors, to reclassify an individual into a higher risk category. Except in the case of evidence of subclinical disease defining the presence of ASCVD, reclassification to a higher risk category is a matter of clinical judgment. Doing so will alter the threshold for consideration of pharmacotherapy and/or the treatment goals for atherogenic cholesterol. Many other ASCVD risk markers are available, but the NLA Expert Panel consensus view is that those listed have the greatest clinical utility.
b Or coronary artery calcium ≥75th percentile for age, sex, and ethnicity. For additional information, see the CAC Score Reference Values web tool (http://www.mesa-nhlbi.org/CACReference.aspx.).
c Because of high intra-individual variability, multiple high-sensitivity C-reactive protein (hs-CRP) values should be obtained before concluding that the level is elevated. hs-CRP should not be tested in those who are ill, have an infection, or are injured. If hs-CRP level is >10 mg/L, consider other etiologies such as infection, active arthritis, or concurrent illness.
Table 10. Diet Characteristics and Diseases/Disorders/Altered Metabolic States That May Elevate LDL-C and/or Triglyceride Concentrations
Cause | Elevate LDL-C | Elevate Triglycerides |
---|---|---|
Diet | ||
Positive energy balance | ✔ | ✔ |
High saturated fat | ✔ | |
High trans fats | ✔ | |
High glycemic load | ✔ | |
Excess alcohol intake | ✔ | |
Weight gain | ✔ | ✔ |
Anorexia nervosa | ✔ | |
Diseases/disorders/altered metabolic states | ||
Chronic kidney disease | ✔ | ✔ |
Nephrotic syndrome | ✔ | ✔ |
Obstructive liver disease | ✔ | |
Diabetes mellitus | ✔ | |
Metabolic syndrome | ✔ | |
HIV infection | ✔ | ✔ |
Autoimmune disorders | ✔ | ✔ |
Hypothyroidism | ✔ | ✔ |
Pregnancy | ✔ | ✔ |
Polycystic ovary syndrome | ✔ | ✔ |
Menopause transition with declining estrogen levels | ✔ | ✔ |
Table 11. Criteria for Clinical Identification of the Metabolic Syndrome (≥3 of the Listed Components)
Measure | Categorical Cut Points |
---|---|
1. Elevated waist circumferencea |
|
2. Elevated triglycerides (drug treatment with a triglyceride-lowering agent is an alternative indicatorb) |
|
3. Reduced HDL-C |
|
4. Elevated blood pressure (antihypertensive drug treatment in a patient with a history of hypertension is an alternative indicator) |
|
5. Elevated fasting glucose (drug treatment of elevated glucose is an alternative indicatorc) |
|
a American Heart Association/National Heart, Lung and Blood Institute guidelines for metabolic syndrome suggest waist circumference thresholds of ≥37 inches (≥94 cm) in men and ≥32 inches (≥80 cm) in women as optional cut points for individuals or populations with increased insulin resistance, including those of Asian descent (alternative values have also been published for other groups).
b The most commonly used drugs for elevated triglyceride levels are fibric acids, nicotinic acid and high-dose long-chain omega-3 fatty acids. A patient taking any of these drugs may be presumed to have an elevated triglyceride level.
c Most patients with type 2 diabetes mellitus will have the metabolic syndrome by these criteria.