Understanding Hyperlipidemia

• Hyperlipidemia refers to elevated levels of lipids in the blood.

When to Screen Cholesterol

• Cholesterol screening can begin at age 20.
• The US Preventive Services Task Force concludes that there is insufficient evidence weighing benefits vs. harms in screening children and adolescents earlier than this.

Standard Lipid Analysis

• A lipoprotein profile measures the level of cholesterol in the blood.
• A fasting sample is preferred for standard lipid analysis but not mandatory.
• It measures total cholesterol, high-density lipoprotein (HDL), triglycerides, and low-density lipoprotein (LDL).
• HDL is "good cholesterol;" high levels protect against coronary heart disease events; low levels (<40mg/dL) increase the risk of heart disease.
• Triglycerides are another type of fat measured.
• Estimated very-low-density lipoprotein cholesterol (VLDL-C) can be calculated by dividing triglycerides by 5 (only if triglycerides <400mg/dL).
• LDL is "bad cholesterol;" high levels circulating in the blood with other substances form interarterial plaques leading to atherosclerosis.

Other Tests

• Lipid/biomarkers are associated with increased atherosclerotic cardiovascular disease (ASCVD) risk, especially in cases of primary hypertriglyceridemia (≥175 mg/dL).
• High-sensitivity C-reactive protein (hs-CRP) ≥2.0 mg/L is a marker of inflammation.
• Elevated Lipoprotein (a) [Lp(a)]is a relative indication of premature ASCVD.
• Apolipoprotein B (apoB) measures the number of cholesterol-laden particles circulating in the blood.
• Elevated apoB ≥130 mg/dL corresponds to an LDL-C >160 mg/dL.
• ABI <0.9 can indicate increased risk.

Other Tests

• The coronary calcium score assesses the amount of calcified plaque in the coronary arteries.
• Calcium Score of 0: <1% 10-year risk CV event, Very low risk interpretation
• Calcium Score of 1-99: 4% 10-year risk CV event, Low risk interpretation
• Calcium Score of 100-399: 13% 10-year risk CV event, Moderate risk interpretation
• Calcium Score of 400 or greater: 24% 10-year risk CV event, High-risk interpretation

Primary Hyperlipoproteinemia

• Primary hyperlipoproteinemia includes conditions like Heterozygous Familial Hypercholesterolemia (HeFH).

Common Secondary Causes of Hyperlipidemia

• Conditions that affect lipids include hypothyroidism and nephrosis.

Treatment

• Lifestyle modifications must be enforced regardless of risk including a heart-healthy diet, regular exercise, avoidance of tobacco products, and maintenance of a healthy weight.

HMG-CoA Reductase Inhibitors (“Statins")

• These inhibit HMG-CoA reductase, the rate-limiting step in cholesterol biosynthesis, decreasing hepatic formation of cholesterol.
• Hepatic LDL-C receptors are upregulated, resulting in further clearance of LDL-C from the systemic circulation.
• Examples of statins include atorvastatin, rosuvastatin, simvastatin, lovastatin, pravastatin, fluvastatin, and pitavastatin.

Side Effects of Statins

• Transaminitis (Elevated Liver Function Tests) is usually reversible with dose adjustment or holding medication.
• Muscle-related side effects range from soreness to rhabdomyolysis (CPK >40 x's upper limit of normal with renal dysfunction).
• Side effects increase with concurrent use of fibrates, niacin, cyclosporine, antifungal agents, protease inhibitors, verapamil, amiodarone, and grapefruit juice.

Statin Potency and Safety

• Rosuvastatin or atorvastatin provides the most potent LDL reduction.
• Atorvastatin or fluvastatin are safest to use in severe renal impairment.
• Pravastatin, fluvastatin, rosuvastatin, and pitavastatin have fewer pharmacokinetic drug interactions.
• Pravastatin and fluvastatin are least likely to cause muscle toxicity.

Statin Therapy

• High-Intensity Statin Therapy lowers LDL-C by approximately ≥50%.
• High-intensity statins include atorvastatin 40 or 80 mg and rosuvastatin 20 or 40 mg.
• Moderate-Intensity Statin Therapy lowers LDL-C by approximately 30% to 49%.
• Moderate-intensity statins include atorvastatin 10 or 20 mg, rosuvastatin 5 or 10 mg, simvastatin 20-40 mg, pravastatin 40 mg, lovastatin 40 mg.

Cholesterol absorption inhibitors

• These block re-uptake of cholesterol in the small intestine which decreases delivery of cholesterol to the liver and upregulation of LDL receptors.
• Ezetimibe (Zetia) is taken 10 mg daily.
• Bempedoic acid and ezetimibe (Nexlizet) is an adenosine triphosphate-citrate lyase (ACL) inhibitor.

PCSK9 inhibitors

• PCSK9 inhibitors increase the number of LDL receptors available to clear LDL, and lowering LDL-C levels.
• Examples include Praluent (alirocumab) and Repatha (evolocumab).

siRNA Therapy

• Small interfering RNA (siRNA) therapy is directed to prevent the production of PCSK9.
• LEQVIO® (inclisiran) is a siRNA injection administered initially, again at 3 months, and then every 6 months.

Fibric Acid Derivatives

• Fibric Acid Derivatives lowers triglycerides and may be helpful if fasting triglycerides are >500 to reduce risk of pancreatitis.
• Drug-Drug reaction Myopathy risk when used with statins (less risk with fenofibrate)

Omega-3 Fish Oil

• Omega-3 Fish Oil is used to treat severe hypertriglyceridemia.
• Prescription Omega-3 oil 2-4g PO daily can lower triglycerides by 27-45%.

Niacin

• Niacin decreases hepatic production of VLDLs and apolipoprotein (apo) B-100, inhibits free fatty acid release from adipose tissue, and stabilizes apo A-1.
• Niacin can increase HDL-C and decrease LDL-C and triglycerides.

Bile acid-binding Agents

• Bile acid-binding Agents interfere with reabsorption of bile acids in intestines.
• Bile acid-binding Agents causes significant bloating and constipation.
• Bile acid-binding Agents include cholestyramine, cholestipol and colesevelam.

Clinical Guidelines

• Guidelines includes a review of lifestyle habits (e.g., diet, physical activity, weight or body mass index, and tobacco use).

Secondary prevention

• Goal is to prevent acute coronary events in patients who already have known Clinical Atherosclerotic Coronary Vascular Disease (ASCVD).

What is Clinical ASCVD?

• Acute coronary syndrome (ACS) or any history of Myocardial infarction (MI).

Very High Risk ASCVD

• Very high risk includes a history of multiple major ASCVD events or one major ASCVD event and multiple high-risk conditions.

Primary Prevention

• The primary goal is Preventing acute coronary events in those patients who do not have clinical ASCVD.

When to start statins in Primary Prevention

• Age 0-19: focus on lifestyle
• Age 20-39, estimate lifetime risk
• Age 40-75, ASCVD Risk assessment
• Age >75, Clinical assessment, risk discussion

Primary Prevention

• In patients with severe primary hypercholesterolemia (LDL-C level ≥ 190 mg/dL[≥4.9 mmol/L]) without calculating 10-year ASCVD risk, begin high-intensity statin therapy.

Primary Prevention

• In patients with diabetes mellitus and LDL-C ≥70 mg/dL (≥1.8 mmol/L), moderate-intensity statin therapy should be initiated without calculating 10-year ASCVD risk.