Dyslipidemia is a metabolic disorder characterized by abnormally high or low amounts of any or all lipids (e.g. fats, triglycerides, cholesterol, phospholipids) or lipoproteins in the blood. which include coronary artery disease, cerebrovascular disease, and peripheral artery disease. Other factors, such as comorbid conditions and lifestyle in addition to dyslipidemia, is considered in a cardiovascular risk assessment. In developed countries, most dyslipidemias are hyperlipidemias; that is, an elevation of lipids in the blood. This is often due to diet and lifestyle. Prolonged elevation of insulin resistance can also lead to dyslipidemia.

  • Erectile dysfunction
  • Chronic kidney disease (eGFR < 60ml/min/1.73 m<sup>2</sup>)
  • Abdominal aneurysm
  • Chronic obstructive pulmonary disease
  • Clinical manifestations of hyperlipidemias (xanthelasmas, xanthomas, premature arcus cornealis)
  • Hypertensive disorders of pregnancy
  • Inflammatory bowel disease

Diagnosis

Classification

Physicians and basic researchers classify dyslipidemias in two distinct ways. One way is its presentation in the body (including the specific type of lipid that is increased). High triglyceride levels (>1.7&nbsp;mmol/L fasting) can indicate dyslipidemia. LDL-C molecules bind to the endothelium of blood vessels and cause plaque formation. In combined hyperlipidemia, there is an overproduction of apoB-100 in the liver. This causes high amounts of LDL and VLDL molecules to form. Some diseases that are associated with a higher risk of dyslipidemia are uncontrolled diabetes mellitus, cholestatic liver disease, chronic kidney disease, hypothyroidism, and polycystic ovarian syndrome. In general, those with a high risk of cardiovascular disease should be screened at a younger age with males between 25 and 30 years old and females between 30 and 35 years of age. Cardiovascular risk can be determined using risk scores, such as the Framingham Risk Score, and should be reassessed every 5 years for patients who are 40 to 75 years of age.

Pharmacological

Pharmacological intervention can be considered in dyslipidemia.

Based on the Framingham Risk Scores, there are different thresholds that indicate whether treatment should be initiated. Individuals with a score of 20% are considered to have a high cardiovascular risk, a score of 10–19% indicates an intermediate risk, and patients with a score less than 10% are at low risk. Statin therapy and non-pharmacological interventions are indicated in those with high cardiovascular risk. In those at intermediate risk or low risk, the use of statin therapy depends on individual patient factors such as age, cholesterol levels, and risk factors.

HMG-CoA reductase inhibitors (statins)

Statins competitively inhibit hydroxymethylglutaryl (HMG) CoA reductase which is used in the biosynthesis of cholesterol and they include atorvastatin, lovastatin, simvastatin, rosuvastatin, pravastatin, fluvastatin, and pitavastatin. These agents work to lower LDL-C levels and are also associated with a decrease in CVD mortality, CVD morbidity, and total deaths. They have a small effect on HDL-C levels as well. Resins include cholestyramine, colestipol, and colesevalem, and they all decrease LDL-C while increasing HDL-C levels slightly. The Lipid Research Council—Cardiovascular Primary Prevention Trial (LRC-CPPT) also showed that when these agents were used alone, they improved cardiovascular outcomes. They include fenofibrate, gemfibrozil, and bezafibrate and work to decrease triglycerides, increase HDL-C, and also decrease LDL-C which is variable depending on which drug is used. The FIELD Study showed that fenofibrate reduced both coronary revascularization as well as nonfatal myocardial infarctions (but not in patients with type 2 diabetes).

PCSK9 inhibitors

PCSK9 inhibitors are monoclonal antibodies that target an important protein in the degradation of LDL called proprotein convertase substilisin/kexin type 9 (PCSK9). These agents reduce LDL-C, increase HDL-C, decrease triglycerides, and decrease lipoprotein(a). The FOURNIER and ODYSSEY trials showed that these agents also reduced the risk of cardiovascular events. Regarding cardiovascular events, patients with chronic kidney disease saw a reduction in vascular and major atherosclerotic events when on simvastatin and ezetimibe compared to placebo. This same combination was also shown to reduce death, major coronary events, and nonfatal stroke in patients after acute coronary syndromes.

Icosapent ethyl

Icosapent ethyl consists of eicosapentaenoic acid (EPA), an omega-3 fatty acid from fish oil and works to lower the hepatic production of triglycerides. In the REDUCE-IT trial, patients on statin therapy and 4g daily of icosapent ethyl saw a reduction in major cardiovascular events.

Microsomal triglyceride transfer protein inhibitors

Lomitapide works to inhibit the microsomal triglyceride transfer protein (MTP) which results in a reduction of LDL plasma levels.

ATP citrate lyase inhibitors

Bempedoic acid acts on the cholesterol synthesis pathway upstream of statins at ATP citrate lyase. This enzyme synthesizes acetyl-CoA using citrate from the mitochondria.

Cholesteryl ester transfer protein inhibitors

Cholesteryl ester transfer protein (CETP) inhibitors include the agents torcetrapib, anacetrapib and obicetrapib. They block transfer of cholesterol from "good" HDL particles to "bad" LDL particles thereby causing an increase in the HDL:LDL ratio. Despite eliciting favorable changes in blood lipids, most CETP inhibitors (with the exception of anacetrapib) do not achieve significant reductions in cardiovascular events.

References

ja:脂質異常症