_______________________________________ Hyperlipidemias and Atherosclerotic Cardiovascular Disease
mipomersen in 2016. Lomitapide and mipomersen inhibit the synthesis of Apo B–100, while bempedoic acid inhibits renal tubular organic anion transporter 2 [109; 110; 233]. Familial hypertriglyceridemia is a common autosomal dominant disease characterized by high triglycerides (200–500 mg/dL or 2.3–5.7 mmol/L) and normal LDL. Lipid-lowering drugs (e.g., fibrates, niacin, statins) combined with diet and weight loss are the most appropriate therapy [30]. SECONDARY HYPERLIPIDEMIAS Secondary hyperlipidemias are associated with primary underlying conditions such as obesity (increased triglycerides and decreased HDL), diabetes (increased triglycerides and increased total cholesterol), alcohol abuse (increased triglycerides and increased HDL), chronic renal insufficiency (increased total cholesterol and increased triglycerides), and hypothyroidism (increased total cholesterol). It has been postulated that these events expose an underlying genetic or metabolic deficiency that increases the individual’s susceptibility to develop hyperlipidemia [31; 100]. Along with polygenic hypercholesterolemia, atherogenic dyslipidemia is one of the most common forms of hyperlipidemias. Atherogenic dyslipidemia is found in approximately 25% of patients with dyslipidemias and is usually diagnosed in patients with metabolic syndrome. In atherogenic dyslipidemia patients there is increased mobilization of triglycerides and cholesterol from adipose tissue to the circulation. This results in increased concentrations of triglycerides and VLDL rich in Apo C-III. Apo C-III inhibits lipoprotein lipase and prevents extraction of triglycerides from VLDL. Moderate-to-high increases in triglycerides (150–500 mg/L or 1.69–5.65 mmol/dL) result from high fat intake and mobilization from adipose tissue and VLDL secretion by the liver. These patients are treated with lifestyle changes aimed at weight reduction and increasing physical activity (which stimulates lipoprotein lipase activity). Statins (to lower VLDL) and fibrates (to lower triglycerides) are the most appropriate drugs to complement lifestyle changes [31; 111]. Studies support the use of antioxidants as well as newer fibrates in the treatment of atherogenic dyslipidemia based on their agonism at the peroxisome proliferator-activated receptor α (PPAR- α ) [112; 113]. Secondary hyperlipidemias can also be associated with a number of drug-induced conditions such as estrogen therapy (increased triglycerides and increased total cholesterol), atypical antipsychotics (increased triglycerides), corticosteroids (increased total cholesterol), selective α -blockers without intrinsic sympathetic activity or α -antagonism (increased total cholesterol and decreased HDL), and thiazides (modest increase in total cholesterol and LDL) [67; 114]. In summary, secondary hyperlipidemias with elevated triglycerides are the primary lipid abnormality in patients with obesity, diabetes, alcohol abuse, hormone replacement therapy, and atypical antipsychotic therapy. Secondary hyperlipidemias
with elevated cholesterol are the main dyslipidemia in patients with chronic renal failure, hypothyroidism, and typical β -blocker use (e.g., propranolol, atenolol). From a clinical perspective, identifying the lipid profile, classifying the hyperlipidemia, and managing comorbidity are each necessary for patients to achieve lower cholesterol and triglyceride levels required to reduce ASCVD risk [22; 25; 46; 100; 105]. APPROACHES TO CLINICAL MANAGEMENT OF HYPERLIPIDEMIAS Management of existing hyperlipidemia is a cornerstone in the prevention and management of ASCVD. In large randomized controlled trials, LDL lowering has been consistently shown to reduce the risk of ASCVD. However, in clinical practice, absolute responses in LDL levels to statin therapy depend on baseline LDL levels and the intensity of lipid-lowering therapy. Furthermore, it is important to bear in mind that as cardiovascular risk increases, so does the absolute benefit of therapeutic interventions proven to lower LDL cholesterol levels; both the absolute risk and the magnitude of LDL cholesterol level reduction achieved are important [235]. A given dose of statins produces a similar percentage reduction in LDL levels across a broad range of baseline levels; therefore, percentage reduction is a more reliable indicator of statin efficacy. The 2018 AHA/ACC guideline uses percentage reduction to estimate the efficacy of statin therapy, with the primary goal being a ≥50% reduction in LDL levels [24].
The U.S. Preventive Services Task Force (USPSTF) recommends that adults without a history of cardiovascular disease (CVD) use a low- to moderate-dose statin for the prevention of cardiovascular events and
mortality when all of the following criteria are met: • They are 40 to 75 years of age. • They have one or more CVD risk factors. • They have a calculated 10-year risk of a cardiovascular event of 10% or greater. Identification of dyslipidemia and calculation of 10-year CVD event risk requires universal lipids screening in adults 40 to 75 years of age. (https://www.uspreventiveservicestaskforce.org/uspstf/ recommendation/statin-use-in-adults-preventive- medication. Last accessed July 24, 2025.) Strength of Recommendation/Level of Evidence : B (There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial.)
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