From the Guidelines
There is no definitive LDL level at which cardiovascular events are completely eliminated, but the most recent evidence suggests that an LDL level below 55 mg/dL is considered optimal for reducing cardiovascular risk, especially in high-risk patients. To achieve this target:
- Use high-intensity statins like atorvastatin 40-80 mg or rosuvastatin 20-40 mg daily
- Add ezetimibe 10 mg daily if needed
- Consider PCSK9 inhibitors for very high-risk patients not reaching goals Lifestyle modifications are also crucial:
- Heart-healthy diet low in saturated fats
- Regular exercise (150 minutes moderate or 75 minutes vigorous activity weekly)
- Smoking cessation
- Stress management Lower LDL levels reduce atherosclerotic plaque formation and progression, as supported by the 2021 European Heart Journal study 1. However, other factors like inflammation, hypertension, and diabetes also contribute to cardiovascular risk. Therefore, a comprehensive approach to cardiovascular health is necessary, even with optimal LDL levels. The goal of treatment is to lower LDL-C to <55 mg/dL and to reduce it by at least 50% if the baseline LDL-C level is 70-135 mg/dL, as recommended by the 2020 ESC guidelines for the management of acute coronary syndromes 1.
From the Research
LDL Level and Cardiovascular Events
- There is evidence that very low LDL cholesterol levels are associated with a very low risk of cardiovascular disease 2.
- Analyses of randomized clinical trials have shown a greater benefit in reducing the risk of cardiovascular disease among those with very low achieved LDL (below 40 mg/dL) 2.
- In one study, patients with achieved LDL cholesterol below 30 mg/dL had no increase in the usual adverse events compared to patients with LDL cholesterol levels above 30 mg/dL 2.
- Some studies suggest that there is no lower limit for LDL-C, and that large, randomized studies and meta-analyses have found continuous benefit and no safety concerns in patients achieving LDL-C levels <25 mg/dL 3.
LDL Targets
- Current guidelines recommend an LDL cholesterol target of 70 mg/dL for patients at high or very high risk 2, 4.
- However, some studies suggest that even lower targets, such as <25 mg/dL, may be beneficial in reducing the risk of cardiovascular disease 3.
- Achieving these targets can be challenging, and several factors, including clinical inertia, non-adherence to prescribed medications, and limited access to add-on therapies, can contribute to the failure to meet LDL-C goals 3, 5.
Cardiovascular Risk Reduction
- Reducing LDL-C levels is a key strategy for reducing the risk of cardiovascular disease, particularly in patients with very high cardiovascular risk 4, 3.
- Early and sustained reductions in LDL-C are critical to slow or halt disease progression in patients with atherosclerotic cardiovascular disease (ASCVD) 3.
- Promoting patient and clinician education, multidisciplinary collaboration, and other interventions may help to overcome the barriers to achieving LDL-C goals and reducing cardiovascular risk 3.