One-third of US adults have elevated low-density lipoprotein cholesterol levels,
More than one-third of patients seen in primary care.
Patients with dyslipidemia also often have associated comorbid conditions and other barriers to treatment that must be considered in the management of the condition.
Dyslipidemia can have either genetic causes referred to as primary dyslipidemia or lifestyle-related causes referred to a secondary dyslipidemia.
The most common primary cause of elevated LDL-C is familial hypercholesterolemia (FH).
The most common primary lipid disorder of childhood is familial hypercholesterolemia, which is present in one in 250 to 350 children.
FH is a frequent cause of premature coronary heart disease (CHD) and can be transmitted in a homozygous or a heterozygous pattern.
Approximately 20% of acute coronary events occurring in persons younger than 45 years in the US general population are attributable to FH.
The prevalence of elevated LDL-C increases with age: about 12% in the 20 to 39 age group, 41.% in the 40 to 64 age group, and 58.%for the 65 and older age group.
Heterozygous FH occurs with a frequency of approximately 1 in 300 to 1 in 500 in the general population.
Homozygous FH occurs in approximately 1 in 1 million in the general population.
In certain special populations such as French Canadians, Christian Lebanese, Dutch Afrikaners, Ashkenazi Jews, and Asian Indians its incidence is higher.
Due to high prevalence of dyslipidemia, all children and adults should be screened for hypercholesterolemia.
It is recommended universal screening with a fasting lipid panel at ages 9 to 11 years to identify all children with genetic causes of hyperlipidemia.
Screening should occur before 2 years of age, if there is a strong positive family history of hypercholesterolemia or premature CHD or the presence of other major CHD risk factors.
The US Preventive Services Task Force strongly recommends screening men aged 35 and older and women aged 45 and older for lipid disorders.
It also recommends screening men aged 20 to 35 years and women aged 20 to 45 years for lipid disorders if they are at increased risk for CHD.
Dyslipidemia is not simply elevated total cholesterol (TC) and triglycerides (TG) numbers or low high-density lipoprotein cholesterol (HDL-C) or LDL-C numbers.
Dyslipidemia and cardiovascular disease are common in shift workers and eating at night may contribute to this pathophysiology: postprandial lipid metabolism, which leads to hypersensitivity in triglyceride responses when eating at night.
The interpretation of dyslipidemia should be individualized, incorporating demographic data and comorbid conditions.
There are 3 broad subclasses of lipoproteins.
Levels of one or more of these lipoprotein subclasses may be abnormal.
Elevated LDL-C is the major risk factor for CHD.
Elevated LDL-C is commonly a result of secondary causes.
Lifestyle interventions are the essential part of management.
Elevated TC and LDL-C suggest the presence of FH.
The probability of the presence of FH is approximately 80% when the LDL-C level is greater than 250 mg/dL in patients aged 30 years or older, greater than 220 mg/dL in patients aged 20 to 29 years, and greater than 190 mg/dL in patients younger than 20 years of age.
A patient with a personal or family history of premature CHD and physical findings of tendinous xanthomas, tuberous xanthomas, or corneal arcus all should warrant suspicion for FH.
Gene mutation is the gold standard for diagnosis of FH.
Only 1in 25 persons in the general population receives a diagnosis of FH, due to the wide variety of secondary causes, dietary effects, and familial polygenic influences.
General population-based studies have shown a US prevalence of FH of 1 in 300 to 1 in 500.
Drug therapy for elevated LDL-C levels includes statins, ezetimibe, and bile-acid sequestrants.
PCSK9 inhibitors are available for the treatment of FH in statin-intolerant patients and patients with CHD who are not at goal LDL-C levels.
The most common causes of hypertriglyceridemia are related to diet and overweight.
A TG level above 1000 mg/dL increases the risk for pancreatitis.
Suspect hyperchylomicronemia if the total cholesterol to TG ratio is greater than 1 to 8.
Hyperchylomicronemia therapy includes a fat-restrictive diet and a carbohydrate-restrictive diet for hypertriglyceridemia.
Diet, physical activity, and weight loss are effective long-term therapies for hypertriglyceridemia.
Pharmacologic therapy for hypertriglyceridemia,includes fibric acid derivatives, fish oils, and niacin.
Bile-acid sequestrants are contraindicated in hypertriglyceridemia because they increase TG levels.
HDL-C is involved in reverse cholesterol transportation.
Low HDL-C levels might be a sign of insulin resistance syndrome.
Most HDL-C treatments should be based on lifestyle interventions such as aerobic and resistance exercises, smoking cessation, weight loss, and a diet rich in monounsaturated or polyunsaturated fatty acids.
The most important reason to treat dyslipidemia is to reduce CHD risk.
Dyslipidemia Clinical Practice Guidelines (2019)
For very-high-risk patients (10-year risk of CV death ≥10%): Use an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.4 mmol/L (<55 mg/dL).
For very high-risk patients who experience a second vascular event within 2 years while taking maximally tolerated statin therapy: An LDL-C goal of below 1.0 mmol/L (<40 mg/dL) may be considered.
For patients at high risk (10-year risk for CV death of 5% to <10%): Use an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 1.8 mmol/L (<70 mg/dL).
For individuals at moderate risk (10-year risk for CV death of 1% to <5%): Consider an LDL-C goal of below 100 mg/dL.
For individuals at low risk (10-year risk for CV death <1%): Consider an LDL-C goal of below <116 mg/dL.
Measurement of lipoprotein(a) (Lp(a)) should be done at least once in each adult’s lifetime to identify those with very high inherited Lp(a) levels above 180 mg/dL (>430 nmol/L) who may have a lifetime risk of atherosclerotic CV disease (ASCVD) that is equivalent to the risk associated with heterozygous familial hypercholesterolemia (FH).
In high-risk patients with triglyceride (TG) levels between 135-499 mg/dL despite statin treatment, consider the combination of n-3 polyunsaturated fatty acids (PUFAs) (icosapent ethyl 2 × 2g/day) with statins.
Treatment of patients with heterozygous Familial hypercholesterolemia should be considered for primary prevention in individuals with FH at very-high risk, consider an LDL-C reduction of over 50% from baseline and an LDL-C goal below 55 mg/dL.
For primary prevention in older people aged up to 75 years, statin therapy is recommended based on the level of risk.
For primary prevention in older people older than 75 years, initiation of statin treatment may be considered if they are at high risk or above.
For patients with type 2 diabetes mellitus (T2DM) at very-high risk, an LDL-C reduction of at least 50% from baseline and an LDL-C goal of below 55mg/dL is recommended.
For those with T2DM at high risk, an LDL-C reduction of at least 50% from baseline and an LDL-C goal of 70 mg/dL is recommended.
For individuals with T1DM who are at high or very-high risk, statins are recommended.
Consider intensification of statin therapy before introducing combination therapy.
If the goal is not reached, consider a statin combined with ezetimibe.
Statin therapy is not recommended in premenopausal diabetic patients who are considering pregnancy.
Lipid-lowering therapy in patients with acute coronary syndromes.
In acute coronary syndrome (ACS)patients and whose LDL-C levels are not at goal despite already taking a maximally tolerated statin dose and ezetimibe, consider adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor early after the event.
The USPSTF concludes that the current evidence is insufficient to establish the benefits/harms of screening for lipid disorders in children and adolescents 20 years or younger.