Inflammation and cardiovascular risk

Risposta: For decades, atherosclerosis was regarded simply as a mere disorder involving lipid deposition, a ‘hydraulic’ process in which cholesterol passively accumulates within the arterial walls until they become obstructed. Today we know that this view is largely outdated: atherosclerosis is, to all intents and purposes, a chronic inflammatory condition of the endothelium and the vascular wall, in which lipids act as the substrate, but inflammation is the true driving force behind its progression and destabilisation.

The process begins when low-density lipoproteins (LDL) penetrate the subendothelial space, where they undergo oxidation. This event attracts monocytes from the bloodstream, which migrate into the arterial wall, transform into macrophages and phagocytose the oxidised LDL until they become ‘foam cells’. This aggregate forms the lipid core of the atherosclerotic plaque. It is the degree of cellular inflammation present within the plaque that determines its fate. A plaque rich in lipids but lacking marked inflammatory activity tends to have a thickened and stable fibrous cap; by contrast, an intense inflammatory response leads to the recruitment of T lymphocytes and the secretion of enzymes (such as metalloproteinases) that degrade the collagen of the fibrous cap. The resulting fissuring or rupture of the plaque exposes the necrotic material to the bloodstream, triggering platelet aggregation and the coagulation cascade, leading to the immediate formation of a thrombus – the primary cause of acute myocardial infarction or ischaemic stroke.

Medicines currently used to lower cholesterol, such as statins, ezetimibe, bempedoic acid, monoclonal antibodies and mRNA-interfering drugs, as well as new molecules used to treat obesity and diabetes (GLP-1 receptor agonists) derive much of their clinical efficacy precisely from their pleiotropic ability to drastically reduce markers of systemic inflammation, such as high-sensitivity C-reactive protein (hs-CRP). Inflammation and traditional risk factors reinforce one another in a vicious circle that accelerates vascular damage.

Clinical research is currently focusing on targeted immunomodulatory therapies: international studies are assessing the efficacy of specific anti-inflammatory drugs in preventing cardiovascular events in high-risk patients. During the acute phase of a myocardial infarction, the use of monoclonal antibodies and infusion therapies designed to rapidly reduce both inflammation and LDL cholesterol levels has been shown to limit the extent of necrotic damage to the myocardium, preserving the heart’s pumping function and significantly improving the patient’s long-term prognosis.