Hyperlipidemias and Atherosclerotic Cardiovascular Disease ________________________________________
PLAQUE DISRUPTION As noted, the lipid core of atherosclerotic plaque is initially surrounded by a thicker fibrous cap that provides some degree of stability. In time, an expanding population of foam cells within the lipid core, combined with extracellular calcification and accumulation of oxidized LDL gradually enlarges the plaque. Interestingly, it has been shown that oxidized LDL promotes apoptosis (i.e., programmed cell death) and causes foam cell death, which leads to plaque necrosis, instability, and increased potential for thrombogenesis [33; 34]. At this stage, plaques further protrude into the lumen and disrupt blood flow. Turbulent blood flow increases shear stress in the periphery of the plaque, known as the shoulder region, further increasing risk of instability, plaque disruption, clot formation, and thrombogenesis. These events are often accompanied by symptoms associated with acute ischemia (e.g., angina, myocardial infarction [MI], intermittent claudication, stroke). Lesions at this stage are able to be detected in angiographic studies and ultrasonography [12; 27; 28; 29; 31; 32].
RISK FACTORS FOR HYPERLIPIDEMIA As discussed, hyperlipidemia has been established as a main risk factor in the development of atherosclerosis and ASCVD. Together with obesity, hypertension, diabetes, smoking, and physical inactivity, hyperlipidemia is a known modifiable risk factor of ASCVD. Additionally, several biomarkers, including C-reactive protein (CRP), hyperhomocysteinemia, and lipoprotein(a), are also considered modifiable risk factors of ASCVD. Modifiable risk factors play a major role in the pathogenesis of ASCVD because they activate the endothelium and stimulate the release of proinflammatory mediators and cell surface adhesion molecules. Because modifiable risk factors account for up to 90% of population-attributable cardiac risk, regulation of these factors has a beneficial effect on the primary and secondary prevention of ASCVD [11; 12]. In addition to modifiable risk factors, the American Heart Association (AHA) and the American College of Cardiology (ACC) have included “risk-enhancing factors” in their 2018 guideline on the management of blood cholesterol ( Table 1 ). Projections of future risk derived from primary risk factors and risk-enhancing factors can be used to adjust the intensity of LDL-lowering therapy and enhance clinician-patient risk discussion [24]. When risk is uncertain, a coronary artery calcium score can help facilitate decision-making in adults
AHA/ACC RISK-ENHANCING FACTORS • Family history of premature ASCVD (men: age younger than 55 years; women: age younger than 65 years) • Primary hypercholesterolemia (LDL 160–189 mg/dL; non-HDL 190–219 mg/dL a ) • Metabolic syndrome • Chronic kidney disease (i.e., eGFR 15–59 mL/min/1.73 m 2 with or without albuminuria, not treated with dialysis or kidney transplantation) • Chronic inflammatory conditions (e.g., psoriasis, rheumatoid arthritis, HIV/AIDS) • History of premature menopause (before 40 years of age) and history of pregnancy-associated conditions that increase later ASCVD risk (e.g., pre-eclampsia) • High-risk race/ethnicity (e.g., South Asian ancestry) • Persistently a elevated, primary hypertriglyceridemia (≥175 mg/dL) and/or other lipid/biomarkers associated with increased ASCVD risk, including (if measured): – Elevated hsCRP (≥2.0 mg/L) – Elevated Lp(a): a relative indication for its measurement is family history of premature ASCVD. Lp(a) ≥50 mg/dL or ≥125 nmol/L constitutes a risk-enhancing factor, especially at higher levels of Lp(a). – Elevated Apo B ≥130 mg/dL: a relative indication for its measurement is triglyceride ≥200 mg/dL. A level ≥130 mg/dL corresponds to an LDL >160 mg/dL and constitutes a risk-enhancing factor – ABI <0.9 a Optimally, three determinations. ABI = ankle-brachial index; Apo B = Apolipoprotein B; eGFR = estimated glomerular filtration rate; HIV/AIDS = human immunodeficiency virus/acquired immunodeficiency syndrome; hsCRP = high-sensitivity C-reactive protein; Lp(a) = lipoprotein(a). Source: [24] Table 1
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