Dyslipidemias represent one of the key modifiable risk factors for atherosclerotic cardiovascular disease (ASCVD), including coronary artery disease, cerebrovascular ischemia, and peripheral arterial disease. Epidemiological data show a clear linear relationship between low-density lipoprotein cholesterol (LDL-C) levels and the incidence of cardiovascular events, confirming LDL-C as the primary causal factor in atherogenesis. In apparently healthy individuals, the risk of developing ASCVD is most often the result of the interaction of multiple risk factors, which forms the basis for assessing and managing overall cardiovascular (CV) risk. Risk factor screening should include lipid profiling in men over 40 years of age and in women over 50 years of age or after early menopause. Risk estimation systems such as SCORE2 and SCORE2-OP (used to calculate the 10-year risk of fatal and non-fatal cardiovascular events, with OP referring to older persons) can contribute to rational therapeutic decisions in order to avoid underor overtreatment. Certain individuals classified as high or very high cardiovascular risk do not require SCORE risk assessment but instead require immediate management of all risk factors. This applies to patients with established cardiovascular disease, diabetes, or chronic kidney disease (CKD). In the last decade, and particularly in the period 2023-2026, significant changes have occurred in international guidelines. According to recommendations of the European Society of Cardiology (ESC), European Atherosclerosis Society (EAS), American College of Cardiology (ACC), American Heart Association (AHA), and American Diabetes Association (ADA), there has been a clear shift toward more aggressive LDL-cholesterol lowering, personalized therapy, and broader use of combination treatment strategies. Early diagnosis and aggressive lipid control remain central components of ASCVD prevention. All these guidelines emphasize the need for earlier, more intensive, and combination therapy to achieve very low levels of atherogenic lipoproteins, with special focus on LDL-C, non-HDL-C (total cholesterol minus HDL cholesterol; includes all atherogenic fractions: LDL, VLDL, IDL, lipoprotein(a)), and apolipoprotein B (ApoB). Advances in understanding lipid metabolism and the availability of new therapies have significantly improved treatment options. This review systematically presents modern principles of diagnosis, classification, treatment, and prognosis of dyslipidemias, along with a comparison of key guideline recommendations. Special attention is given to novel therapeutic modalities, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Particular emphasis is also placed on RNA interference gene therapy, where cells can "silence" specific genes via small interfering RNA (siRNA), which represents the mechanism of action of inclisiran.
Babić et al. (Thu,) studied this question.
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