From the Guidelines
Lowering LDL cholesterol to very low levels, such as 35 mg/dL, can indeed result in plaque regression in coronary arteries, as evidenced by studies suggesting that atherosclerosis regression continues as LDL cholesterol levels reach 0.39 mmol/L (15 mg/dL) 1.
Mechanism of Plaque Regression
The mechanism behind this regression involves reduced cholesterol deposition in arterial walls, enhanced cholesterol efflux from plaques, decreased inflammation, and improved endothelial function. Animal data suggest that dramatic LDL cholesterol reduction early in the course of atherosclerosis can completely regress atherosclerosis and normalize arterial function 1.
Treatment Approach
Intensive LDL lowering with high-potency statins, often combined with ezetimibe or PCSK9 inhibitors, has been shown to not only halt atherosclerosis progression but actually reverse it in many patients. This typically requires sustained very low LDL levels over 1-2 years minimum. The use of maximally tolerated statins, ezetimibe, and new drugs such as PCSK9 or CETP inhibitors to dramatically reduce LDL cholesterol may have profound effects on atherosclerosis stabilization and regression 1.
Monitoring and Side Effects
Side effects of such intensive therapy may include muscle symptoms, slightly increased diabetes risk, and liver enzyme elevations, requiring regular monitoring. Regular lipid panels every 3-6 months are necessary to ensure LDL targets are maintained. Not all patients achieve regression even at these low LDL levels, as plaque composition, duration of therapy, and other risk factors like hypertension and diabetes also influence outcomes.
Clinical Implications
The opportunity exists to explore new approaches to cardiovascular prevention, including long-term follow-up of statin trials and the ongoing CVD outcomes trials of new agents, which will help characterize the legacy effect of plaque stabilization and regression in high-risk patients 1. This suggests that early, aggressive LDL cholesterol lowering can reset the vascular aging clock, and intermittent retreatment every decade or so might, in essence, “cure” atherosclerosis.
From the Research
Plaque Regression and LDL Levels
- The relationship between lowering LDL levels and plaque regression is complex, with various studies investigating the effects of different treatments on LDL levels and plaque formation 2, 3, 4, 5.
- A study published in 2014 found that intensive lowering of LDL-C, with a mean reduction of 45.4% and to a level of 66.8 mg/dL, could significantly reduce the volume of coronary atherosclerotic plaques (CAP) at follow-up 2.
- The same study found that LDL-C lowering by rosuvastatin (mean 33 mg daily) and atorvastatin (mean 60 mg daily) could significantly decrease the volumes of CAP at follow-up, with a mean duration of follow-up of 17-21 months 2.
- Another study published in 2015 found that high-intensity statins, such as rosuvastatin 20-40 mg and atorvastatin 40-80 mg, could reduce LDL-C by ≥50% in patients with atherosclerotic cardiovascular disease (ASCVD) 3.
- However, the studies do not provide direct evidence on the specific effect of lowering LDL to 35 on plaque regression.
LDL Reduction and Treatment
- Several studies have compared the efficacy of different statins, such as rosuvastatin and atorvastatin, in reducing LDL-C levels 3, 4, 5.
- A study published in 2022 found that rosuvastatin was significantly more efficacious than atorvastatin in reducing LDL-C in patients with type 2 diabetes mellitus 4.
- Another study published in 2008 found that rosuvastatin 10 mg/day was more efficacious than atorvastatin 20 mg/day in reducing plasma LDL-C levels in patients with primary hypercholesterolemia 5.
- However, the optimal LDL level for plaque regression is not clearly established, and more research is needed to determine the specific effects of lowering LDL to 35 on plaque regression.