Dyslipidemia

Dyslipidemia is a condition where a person exhibits altered blood lipid metabolism. This shows up on bloodwork as abnormal levels of various cholesterols and/or fats, such as high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, and triglycerides.^[1] Non-HDL cholesterol (Non-HDL-C), apolipoprotein B, and the ratio of total cholesterol to HDL-C may also be important metrics to examine in dyslipidemia.^[2][3] Abnormalities in these markers and/or ratios are associated with increased risk of cardiovascular disease.^[4] Changing certain markers may result in stronger clinical outcomes (non-HDL-C) than others (HDL-C).^[5]

Signs of dyslipidemia are easily found on routine blood work. Symptoms of dyslipidemia on its own are rare. Infrequently, people may find xanthomas (hard fatty deposits of tissue on the skin or just under the skin) on their palms, eyelids, or tendons.^[6]

Due to the rarity of dyslipidemia symptoms, and the common presence of other cardiovascular disease risk factors, clinicians will also often examine for high blood pressure, high blood sugar, and obesity if dyslipidemia is suspected.^[7]

Diagnosis of dyslipidemia is based on blood lipid levels. Dyslipidemia includes a wide range of abnormalities of lipid metabolism, and may be diagnosed by a combination of the following:

• Total cholesterol over 240 mg/dL
• LDL-C over 160 mg/dL
• Triglycerides over 200 mg/dL
• HDL-C under 40 mg/dL ^[7]

What are some of the main medical treatments for dyslipidemia? First-line medical treatments for dyslipidemia include lifestyle-based interventions; nutrition, exercise, avoiding tobacco, and weight loss are important first considerations when discussing dyslipidemia treatment.^[7]

Some of the following drugs and therapeutics may be recommended based on a patient's overall risk of cardiovascular disease and individual presentation:^[7]

• Statins are very effective at reducing LDL-C, and have shown a reduction in cardiovascular events (i.e., heart attacks and strokes)^[8]
• PCSK9 inhibitors have also shown these effects, but are more expensive, and have a smaller body of research^[9]
• Ezetimibe may be useful in addition to a statin if further risk reduction is required ^[10]
• Fibrates are recommended for moderate and severe elevations of triglycerides (> 400 to 500 mg/dL)^[11]
• Bile acid sequestrants, such as cholestyramine, may effectively lower LDL-C; however, they may raise triglycerides, there is sparse data for cardiovascular event reductions when used in conjunction with statins, and poor adherence has been noted^[12]
• Folic acid may lower triglycerides and total cholesterol, and was found to increase HDL in a dose-response fashion^[13]
• Niacin may cause robust improvements in HDL-C of 21%; however, there is mostly consistent evidence showing a lack of reduction in cardiovascular events or mortality^[14][15][16]
• Bempedoic acid shows promise for further reducing LDL-C when patients are on a maximally tolerated dose of statins, while not worsening muscular adverse events typical of statins^{[17][18][19][20]}

Omega-3 fatty acid supplements, like fish oil, have been studied for dyslipidemia. They have reliably been found to result in relatively large reductions in triglycerides, and inconsistently increase LDL-C and HDL-C to a minor degree.^[21][22][23] They may increase bleeding risk, so those on anticoagulant drugs should be cautious of taking these supplements.^[7]

Another supplement that has been studied for dyslipidemia is red yeast rice. Red yeast rice sometimes contains monacolin K, which is identical to the statin lovastatin. For this reason, red yeast rice products containing non-negligible amounts of monacolin K are banned by the FDA since they are a “non-approved drug”.^[24][25] If monacolin K is present, red yeast rice may have similar effects and safety profiles to statins.^[26][27] However, the methodology for assessing safety in trials is often poor.^[27]

Additionally, garlic supplements decrease total cholesterol and LDL-C, though not consistently, with unclear impacts on HDL-C.^[28][29] Effects on LDL-C and HDL-C may occur less often when garlic supplements are given alongside a lipid-lowering diet.^[30][31][32].

Finally, psyllium fiber can have beneficial effects not only on LDL-C, but on non-HDL-C and apolipoprotein B levels, which may be more predictive of cardiovascular disease than LDL-C.^[3]

Dietary changes can substantially impact a range of lipid markers, including total cholesterol, LDL-C, and triglycerides.^[1][33][34] Dietary changes may also alter HDL-C levels, but how this impacts cardiovascular health is unclear.^[35]

Generally, dietary changes to improve dyslipidemia encompass encouragement of a caloric deficit (if weight loss is indicated), reduction of saturated fat to <10% of daily calories, increase in monounsaturated fatty acids (MUFA), increase in polyunsaturated fatty acids (PUFA), and an increase in soluble fiber intake.^[1][7] Curtailing heavy alcohol consumption is also recommended, if applicable.^[36]

Exercise can impact several markers of dyslipidemia. Exercise is a commonly recommended therapy to increase HDL-C, but it also can lower LDL-C and triglycerides. ^[37][38]

HDL-C may increase with activity level in a dose-response manner. Decreases in LDL-C and triglycerides may require higher intensity exercise. Aerobic exercise generally has a larger evidence base for encouraging these changes, though resistance exercise may be equally effective as long as it is of a similar caloric expenditure (generally requiring lower weight, more repetitions, and more sets).^[39]

Tobacco smokers have higher levels of triglycerides, LDL-C, and lower levels of HDL-C.^[40] Smoking cessation tends to improve HDL-C within about a year.^[41] There are mixed results as to whether, when, and by how much other blood lipids levels may improve.^[42][4][40] However, smoking cessation clearly does ultimately reduce cardiovascular disease risk.

Obstructive sleep apnea generally increases risk for dyslipidemia.^[43] Fortunately, the gold standard treatment for sleep apnea, continuous positive airway pressure (CPAP) therapy, improves total cholesterol, LDL-C, and HDL-C levels.^[44]

Dyslipidemia can have many causes, including diabetes, tobacco usage, liver and kidney disease, and hypothyroidism.^[7]

There are also different drugs that can cause dyslipidemia:

• Thiazide diuretics
• β-blockers
• Cyclosporine
• Glucocorticoids
• Oral estrogens ^[45]

Finally, there are genetic conditions that can cause dyslipidemia. For example, familial hypercholesterolemia causes high levels of cholesterol from an inability to metabolize LDL-C properly.^[46]