Cholesterol-Lowering Medications for Heart Protection

Heart disease, particularly as a result of atherosclerosis, continues to be the leading cause of death in Germany, with one in three adults facing high cholesterol levels. This condition is a significant risk factor for atherosclerosis, which can lead to coronary heart disease, heart attacks, strokes, and peripheral artery disease.

Atherosclerosis is characterized by the chronic inflammation of medium-sized arteries due to lipid-rich plaque accumulation in the intima. This condition develops over decades, often asymptomatically, and is typically only recognized through clinical events such as myocardial infarction, ischemic stroke, or peripheral artery disease.

The initial stages of atherosclerosis occur at hemodynamically stressed sites, such as at arterial bifurcations, where turbulent blood flow prevails. Cholesterol-rich low-density lipoprotein (LDL) particles infiltrate the subendothelial space, binding to proteoglycans in the extracellular matrix. Risk factors like hypertension, diabetes, and smoking exacerbate this infiltration.

Within the subendothelial compartment, LDL particles undergo mild oxidation due to reactive oxygen species. Oxidized LDL promotes the adhesion of monocytes to the endothelium, which then migrate into the subendothelial space, differentiating into macrophages. These macrophages engulf oxidized LDL, transforming into cholesterol-laden foam cells, which contribute to early fatty streak lesions within the arterial lumen.

As foam cells undergo apoptosis, they release pro-inflammatory cytokines such as IL-6, TNF-?, and IFN-?, perpetuating the chronic inflammatory response within the arteries. Concurrently, smooth muscle cells from the media dedifferentiate, becoming proliferative, and migrate into the intima, where they, along with fibroblasts, proliferate.

Both cell types synthesize components of the extracellular matrix, including collagen, which assists in forming a cap that stabilizes the plaque. This cap conceals the necrotic core, consisting of dead foam cells, cholesterol, and cellular debris. The resulting plaque continues to expand into the arterial lumen, increasing the risk of acute cardiovascular events.

To mitigate these risks, lifestyle modifications, such as weight reduction, increased physical activity, and a balanced diet, are fundamental components of lipid-lowering therapy. However, many patients require additional lipid-lowering medications to manage their cholesterol levels effectively.

Among the available pharmacological options, ezetimibe, PCSK9 inhibitors like alirocumab and evolocumab, and bile acid sequestrants are commonly utilized. Inclisiran, a newer PCSK9 inhibitor, and evinacumab for patients with homozygous familial hypercholesterolemia, are also notable advancements in lipid management.

It is essential for healthcare providers to evaluate the individual needs of patients and consider the potential side effects associated with these medications, particularly regarding muscular health. Continued research and patient education are vital to optimize treatment strategies and improve cardiovascular outcomes.