While screening of all children for cholesterol disorders remains controversial, all adults should have their lipids checked before middle age. Patients with CVD and diabetes deserve the most scrutiny of their lipids since these patients are at the highest risk for suffering additional manifestations in the near term and thus have the most to gain from lipid lowering. Additional risk reduction measures for atherosclerosis are discussed in Chapter 10; lipid lowering should be just one aspect of a program to reduce the progression and effects of atherosclerosis.
The best screening and treatment strategy for adults who do not have ASCVD is less clear. Several algorithms have been developed to guide the clinician in treatment decisions, but management decisions must always be individualized based on the patient’s risk to maximize net benefit.
The 2018 American Heart Association/American College of Cardiology (AHA/ACC)/Multi-society guidelines recommend screening of all adults aged 20 years or older for high blood cholesterol. The 2016 United States Preventive Services Task Force (USPSTF) guidelines recommend beginning at age 20 years only if there are other cardiovascular risk factors such as tobacco use, diabetes, hypertension, obesity, or a family history of premature CVD. For men without other risk factors, screening is recommended beginning at age 35 years. For women and for men aged 20 to 35 without increased risk, the USPSTF makes no recommendation for or against routine screening for lipid disorders. Although there is no established interval for screening, screening can be repeated every 5 years for those with average or low risk and more often for those whose levels are close to therapeutic thresholds.
Individuals without CVD should have their 10-year risk of CVD calculated, with lifetime risk also considered. Although those with LDL cholesterol greater than 190 mg/dL (4.91 mmol/L) are recommended for treatment independent of their 10-year risk of CVD, all other patients are recommended for treatment based on their overall cardiovascular risk. While other calculators (such as SCORE or QRISK) may be more appropriate for other parts of the world, the best method for estimating 10-year risk in the United States is the Pooled Cohort Equations. First introduced in the 2013 ACC/AHA guidelines, the Pooled Cohort Equations include separate equations for white and black patients and estimate the 10-year risk of heart attack, stroke, and cardiovascular death. This represents an improvement over older Framingham 10-year calculator (eTable 28–2), which includes CHD but not stroke risk. The ACC/AHA risk estimator can be found at http://www.cvriskcalculator.com/, and mobile apps are available for download. While it has been shown to overestimate risk in some modern populations, including those with at least moderate socioeconomic status, the ACC/AHA risk estimator remains an excellent starting point for a risk discussion. Recalibrated versions of the calculator are available for countries across the world. The LIFE-CVD model is the best for illustrating lifetime risk and benefit of therapy (https://www.u-prevent.com/en-GB/HealthyCalculator/HealthyCalculator).
eTable 28–2.Framingham 10-year coronary heart disease risk projections. Calculate the number of points for each risk factor. Sum the total risk score and estimate the 10-year risk. ||Download (.pdf) eTable 28–2. Framingham 10-year coronary heart disease risk projections. Calculate the number of points for each risk factor. Sum the total risk score and estimate the 10-year risk.
Shared decision making is a central part of cholesterol management in primary prevention. Therefore, the 2018 AHA/ACC/Multi-society guidelines and the 2019 ACC/AHA primary prevention guidelines identify a set of “risk-enhancing factors” that might influence a clinician and patient to favor cholesterol-lowering treatment. Table 28–1 lists these risk-enhancing factors that may be considered, particularly for patients at borderline to intermediate risk (5–20% 10-year cardiovascular risk).
Table 28–1.Risk-enhancing factors that help identify patients who may benefit most from lipid-lowering therapy: 2018 AHA/ACC/Multi-society guidelines. ||Download (.pdf) Table 28–1. Risk-enhancing factors that help identify patients who may benefit most from lipid-lowering therapy: 2018 AHA/ACC/Multi-society guidelines.
Family history of premature disease (males, age < 55 years; females, age < 65 years)
Primary hypercholesterolemia (LDL cholesterol, 160–189 mg/dL [4.1–4.8 mmol/L]; non–HDL cholesterol, 190–219 mg/dL [4.9–5.6 mmol/L])
Chronic kidney disease (not end-stage renal disease)
Chronic inflammatory conditions, such as psoriasis, rheumatoid arthritis, or HIV/AIDS
History of preeclampsia or of premature menopause before age 40 years
High-risk race/ethnicities (eg, South Asian ancestry)
Persistently high triglycerides ≥ 175 mg/dL
Elevated high-sensitivity C-reactive protein (≥ 2.0 mg/L)
Elevated lipoprotein(a) (≥ 50 mg/dL or ≥ 125 nmol/L)
Elevated apolipoprotein B (≥ 130 mg/dL)
Ankle brachial index < 0.9
Importantly, the 2018 AHA/ACC/Multi-society guidelines and the 2019 ACC/AHA primary prevention guidelines also identify the coronary artery calcium score as the single best test for additional risk stratification. The coronary calcium score is a simple noncontrast cardiac-gated CT scan that takes about 10–15 minutes to do, is associated with approximately 1 mSv of radiation, and costs between $75 and $300. As opposed to the risk-enhancing factors, which may incline a clinician and patient toward treatment, the coronary artery calcium score may also help identify patients who are unlikely to benefit from cholesterol-lowering therapy. For example, when the coronary artery calcium score is zero in the absence of smoking or diabetes, the patient is low risk and less likely to receive net benefit from therapy; instead, the calcium artery calcium score can be repeated in approximately 5 years. The USPSTF does not endorse calcium scoring as a broad screening test; rather the test should be reserved for situations in which additional data will inform shared decision making and potentially change a therapeutic decision.
Statins are nearly always the first-line therapy. Treatment decisions are based on the presence of clinical CVD or diabetes, LDL cholesterol greater than 190 mg/dL (4.91 mmol/L), patient age, and the estimated 10-year risk of developing CVD. The 2018 AHA/ACC/Multi-society guidelines define four groups of patients who benefit from statin medications: (1) individuals with clinical ASCVD; (2) individuals with primary elevation of LDL cholesterol greater than 190 mg/dL (4.91 mmol/L); (3) individuals aged 40–75 with diabetes and LDL greater than or equal to 70 mg/dL (1.81 mmol/L); and (4) individuals aged 40–75 without clinical ASCVD or diabetes, with LDL 70–189 mg/dL (1.81–4.91 mmol/L), and estimated 10-year CVD risk of 7.5% or higher.
Ezetimibe and PCSK9 inhibitors have the strongest recommendations as second-line therapy for patients with (1) CVD whose LDL on statin therapy remains above the 70 mg/dL treatment threshold or (2) possible familial hypercholesterolemia with baseline LDL greater than 190 mg/dL (4.91 mmol/L) whose LDL remains above the 100 mg/dL treatment threshold. In high-risk patients, ezetimibe therapy is favored in part due to reduced cost, while in very high-risk patients, PCSK9 inhibitor therapy should be considered.