Can clogged blood vessels be cleaned up again?

Atherosclerosis (fatty build-up in artery walls) is not a one-way street. In the PESA study, in which more than 3,400 participants were followed for six years, plaque shrank in 8% of people with early atherosclerosis. That percentage may seem small, but it proves that shrinkage is genuinely possible in humans, not just in animal research.

The strongest drivers of plaque growth are excessively high LDL cholesterol (the 'bad' cholesterol) and high blood pressure. Notably, this effect was greatest in the youngest participants, aged 40 to 45. Intervening early therefore yields more benefit. It is also striking that nearly half of the people without classic risk factors already turned out to have atherosclerosis, and that LDL contributed to more extensive plaques even within officially 'normal' ranges. Current threshold values may be too lenient.

Statins, particularly at high doses, measurably reduce the fat content of plaques. They also make plaques less dangerous in terms of their composition. Newer agents called PCSK9 inhibitors have a comparable or stronger LDL-lowering effect and also show plaque shrinkage in imaging studies. There is, however, an important caveat: the direct link between plaque shrinkage on a scan and fewer heart attacks or strokes in practice has not yet been well established.

How plaques shrink is partly understood. Immune cells in the vessel wall store fat when LDL is high, but when LDL is sufficiently lowered they can also export fat and leave the plaque. HDL cholesterol ('the good kind') assists in this process by removing fat from those immune cells. Larger, long-established plaques respond less well to these changes than early plaques do. Anti-inflammatory agents can also reduce plaque, but the evidence for this is thinner than for statins and PCSK9 inhibitors.