Cholesterol is a waxy, fat-like substance found in all cells, necessary for making hormones, Vitamin D, and digestive substances. The two main types are low-density lipoprotein (LDL), often called “bad” cholesterol, and high-density lipoprotein (HDL), or “good” cholesterol. For decades, managing these lipid levels has been the primary strategy for reducing the risk of heart disease and stroke. This management approach has evolved significantly, moving from strict targets to a broader risk-based philosophy.
The Dominance of LDL Targets
The previous guidelines, primarily the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) published in 2002, established LDL cholesterol as the primary focus of therapy. This approach was defined by a “treat-to-target” model, where the goal was to lower a patient’s LDL level to a specific, predetermined number linked to their calculated risk for coronary heart disease (CHD) events.
For patients diagnosed with CHD or those at the highest risk, the initial target was below 100 milligrams per deciliter (mg/dL). A 2004 update suggested an optional goal under 70 mg/dL for “very high-risk” individuals, such as those with multiple major risk factors or acute coronary syndrome.
The guidelines set different thresholds for lower-risk individuals. Patients with two or more risk factors aimed for an LDL level below 130 mg/dL, while those with zero or one risk factor aimed for under 160 mg/dL. Treatment involved initiating and adjusting statin therapy until the specific LDL target was met.
Risk Assessment Under the Former Approach
Under the old guidelines, risk assessment categorized patients to assign the correct LDL target. The cornerstone of this classification was the Framingham Risk Score (FRS), which calculated an individual’s estimated 10-year risk of experiencing a “hard” coronary heart disease event, such as a heart attack or cardiac death. The FRS utilized factors including age, total cholesterol, HDL cholesterol, systolic blood pressure, smoking status, and medication use to generate a percentage risk.
The guidelines also recognized “Risk Equivalents,” which automatically placed a patient into the highest-risk category, regardless of their calculated FRS percentage. These equivalents included established atherosclerotic diseases, such as symptomatic carotid artery disease or peripheral arterial disease, or a diagnosis of diabetes mellitus. A 10-year CHD risk over 20% also qualified as a risk equivalent.
This risk stratification determined the intensity of the treatment plan, but it was secondary to establishing the numerical LDL goal. For instance, a patient with a CHD risk equivalent was immediately assigned the most aggressive LDL target of less than 100 mg/dL.
The Paradigm Shift and Rationale for Change
The move away from the older guidelines, beginning around 2013, was driven by the realization that the treat-to-target approach lacked strong scientific backing from randomized controlled trials (RCTs). While many studies showed that lowering LDL cholesterol with statins reduced cardiovascular events, there was limited evidence proving that adjusting a statin dose to hit a specific, arbitrary LDL number improved outcomes more than simply giving a fixed, effective dose. The focus on achieving a target sometimes led to complex medication regimens without a proven benefit over simpler treatment plans.
Evidence began to show that the intensity of the statin therapy itself, rather than the final LDL level achieved, was the more reliable predictor of reduced cardiovascular risk. Randomized trials demonstrated that fixed doses of moderate- or high-intensity statins provided a consistent benefit regardless of whether the patient’s LDL hit a specific target value. This suggested that the clinical benefit was more closely tied to the overall percentage reduction in LDL and the drug’s properties than to a single numerical threshold.
The newer guidelines abandoned the treat-to-target model entirely and instead focused on identifying “Statin Benefit Groups” based on absolute risk and existing conditions. This new approach emphasizes prescribing a fixed, appropriate intensity of statin based on a patient’s overall risk profile, such as those with existing atherosclerotic disease or very high LDL levels, rather than titrating the dose to chase a specific LDL number.