Regularly, patients presenting with underlying hyperlipidemia remain asymptomatic, therefore obtaining a precise and thorough history is essential. Upon taking a patients history, it is crucial to obtain a profound understanding of each patient’s family history of cardiovascular disease, hyperlipidemia, and/or familial hypercholesterolemia; their diet and exercise habits; tobacco, alcohol, or drug use; the presence of coronary artery disease; risk factors or history of CAD; and/or symptoms of peripheral arterial disease or angina[4]

In addition to obtaining a detailed history, a focused physical exam is also very important. Obtaining accurate blood pressure measurements, observing the patients skin for xanthomas, listening for carotid and femoral bruits for evidence of stenosis, listening for an S4 heart sound, and palpating for intact peripheral pulses in all four extremities are fast and simple physical exam findings that can assist in your diagnosis of hyperlipidemia[1]

Various experts have developed lipid screening guidelines that include the "lipid profile" to measure cholesterol and triglyceride levels. Guidelines differ as to what age primary providers should start screening and how often they should screen patients for hyperlipidemia. In general, it is advised that routine lipid screening should occur when a male turns 35 years of age (if no other cardiovascular risk factors) or 25 years of age (if the patient has other cardiovascular risk factors). It is also suggested that routine lipid screening be initiated in females at 45 years of age (if no other cardiovascular risk factors present) or 30 to 35 years of age (if the patient has other cardiovascular risk factors)[1] For lower-risk patients, lipid screening every five years is reasonable, and more frequent screening is recommended as the patient's cardiovascular risk increases.

As stated above, the most valuable laboratory test to collect is checking fasting lipid profile, which routinely includes LDL, HDL, triglycerides, and total cholesterol. A v-LDL, total cholesterol: HDL, and LDL: HDL ratios can be added on for a more comprehensive test. It is necessary to not eat or drink anything besides water for 9 to 12 hours as not to skew the results of the lipid panel (mainly the triglyceride levels).[4] 

Before starting a statin for high LDL levels, it is important to obtain liver function tests to ensure there is no prior liver dysfunction, as statins may exacerbate this issue. For risk stratification purposes, a Hgb A1c level is necessary to screen for diabetes mellitus, and the clinician should always examine blood pressure measurements to ensure the patient does not have underlying hypertension. Additionally, a TSH should be ordered to rule out underlying thyroid abnormalities, and a simple urinalysis can be collected to screen for albuminuria. These tests are critical for risk-stratification of your patient to accurately assess the potential risks versus benefits of initiating medical therapy in a patient with hyperlipidemia.

The decision to treat elevated LDL cholesterol levels depends on the determination of overall cardiovascular risk by the patient's primary physician, and this should be discussed in great detail with the patient. The absolute risk reduction affiliated with lipid-lowering therapy for hyperlipidemia is generally less than for patients with known underlying cardiovascular disease. To reduce risk in patients without a known diagnosis of cardiovascular disease, only treatments of elevated LDL cholesterol have proven to be of clinical benefit. There is no proven clinical benefit to the treatment of hypertriglyceridemia or low HDL cholesterol levels.[5]

Initial treatment modalities are focused on diet and lifestyle modification, with the possible addition of lipid-lowering medications if needed. Patients with mild hyperlipidemia and low ASCVD risk (below 7.5% 10-year risk) should focus on a low fat, low carbohydrate diet, and moderate to high-intensity physical activity (recommended 30 minutes per day, 5 to 6 days per week). The AHA advises limiting saturated fat consumption to about 5% of your daily calories and restricting the total quantity of trans-saturated fat consumption as much as possible. Quitting smoking, lowering blood pressure, and losing weight have all proven to be very advantageous in regards to lowering vascular disease risk. For patients at moderate to high ASCVD risk (over 7.5% 10-year risk), the addition of lipid-lowering "statin" medications should be added.[6] 

The most well rounded and complete meta-analysis investigating primary prevention trials in hyperlipidemia patients discovered an all-cause mortality benefit and that lowering LDL cholesterol is effective at decreasing cardiovascular events, in particular, reducing the risk of myocardial infarction. There is a clear and proven benefit to statin therapy for the vast majority of patients, from low risk to high risk, and if side effects and financial constraints did not exist, almost all patients would be prescribed statin therapy. Therefore, these medication's side effects and costs should be weighed against the individual patient's potential benefit from taking the drug.

Key Recommendations for Practice: SORT evidence rating system [7]:

• Patients with a high risk of ASCVD (>7.5% 10-year risk) should receive statin therapy for primary prevention: Rating B.
• Statin therapy should be initiated for secondary prevention in patients with known ASCVD, absent any contraindication: Rating A
• Niacin, fibrates, and omega-3 fatty acids should not be routinely given for primary or secondary prevention of ASCVD: Rating A
• A moderate-intensity statin plus ezetimibe should merit consideration as an alternative in patients with acute coronary syndrome who cannot tolerate high-intensity statin therapy: Rating B.
• Moderate-intensity statins include: lovastatin 40 mg, pravastatin 40 mg, simvastatin 40 mg, atorvastatin 10 to 20 mg, and rosuvastatin 5 to 10 mg
• High-intensity statins include: atorvastatin 40 to 80 mg, rosuvastatin 20 to 40 mg

If the provider and patient reach a mutual decision to initiate medical therapy with statins, the overall risk reduction in cardiovascular events is customarily around 20 to 30% in most clinical trials. The commonly referred to trials of which the majority of guidelines are based, included pravastatin 40 mg, lovastatin 20 to 40 mg, atorvastatin 10 mg, and rosuvastatin 10 mg, so general recommendations are to choose one of these statins listed.[5] It is always important to schedule close follow up with patients that are starting lipid-lowering statin therapy. The vast majority of benefits arising from statin therapy originates from the moderate dose, with a much more diminutive benefit deriving from the addition of high-intensity therapy. However, the benefit of high-intensity therapy remains clinically significant and should merit consideration for all high-risk patients.

If a patient encounters an allergy or intolerance to a statin medication, the suggestion is to reduce the original or to transition to a different lipid-lowering medication altogether. Among patients that have reported muscle-related statin intolerances, according to one 24 week trial, evolocumab (PCSK9 inhibitor) reduced LDL cholesterol levels significantly more when compared to ezetimibe.[8] However, both of these medications are reasonable secondary options for treatment.

It is imperative for diagnosing providers to assemble a comprehensive list of differentials when screening a patient for hyperlipidemia. Primary disorders should always be considerations; these include familial hypercholesterolemia, familial combined hyperlipidemia, dysbetalipoproteinemia, familial defective apo B-100, and PCSK9 gain of function mutations.

Then, these secondary disease processes must also be in the differential when diagnosing a patient with hyperlipidemia: obstructive liver disease or biliary obstruction, hypothyroidism, nephrotic syndrome, chronic renal insufficiency, anorexia, obesity, metabolic syndrome, and diabetes.[4] A full history and physical complete with comprehensive labs should be obtained to narrow down the differential and make the correct diagnosis.

Hyperlipidemia is often a life-long disease process, but one that is typically quite manageable. However, if hyperlipidemia is left untreated, the disease is progressive and will often lead to severe underlying vascular disease processes, which can prove fatal. Ongoing persistent exposure to high serum lipid levels throughout early adulthood increases the person's subsequent risk of coronary heart disease in a dose-dependent fashion.[9]

Adults with ongoing exposure to moderate or severe elevations in non-HDL cholesterol levels have concurrent elevated risks for developing coronary heart disease and would likely benefit from aggressive medical treatment modalities, including, which includes high-intensity statin therapy in addition to diet and lifestyle modifications. Based on a 20 year follow up of the "West of Scotland Coronary Prevention Study," the researchers noted that patients who received statin therapy for five years had improved survival rates and a clinically significant reduction in cardiovascular disease over the 20 years. This data supports the numerous other studies and trials that also reveal a significant cardiovascular risk reduction when using statin therapy appropriately, and there was the implementation of a proactive treatment approach.[10]

Complications from undertreated or untreated hyperlipidemia include all types of vascular disease, which may prove fatal down the road. These include, but are not limited to, coronary artery disease, peripheral artery disease, cerebrovascular accidents, aneurysms, type II diabetes, high blood pressure, and even death.[10]

Statin medication complications include myopathy, renal injury, arthralgia, extremity pains, nausea, myalgia, elevated liver enzymes/hepatotoxicity, diarrhea, and rhabdomyolysis. Reportedly up to 5 to 20% of patients taking a statin medication experience a muscle-related intolerance.[8] A lower dose of the statin should be attempted and/or attempting to transition to another lipid-lowering medication such as ezetimibe or evolocumab.

Aerobic exercise has shown to increase the levels of the HDL-cholesterol protein, with an anti-atherogenic action: the HDL that transports cholesterol from the walls of the arteries and peripheral tissues to the liver and the same HDL has an antioxidant and anti-inflammatory capacity that induces the release of nitric oxide (vasodilator compound). Estimates are that adding 10 minutes of physical activity to daily exercise increases the concentration of HDL by 1.4 mg/dl, and it has been calculated that, on average, an adequate training program can increase cholesterol HDL of 4.6%.[11]

A combination of aerobic and anaerobic activity is equally capable of positively influencing blood lipid levels.[12]

One hour per week of resistance training (anaerobic activity) can improve the lipid profile and corresponds to a correct indication in order not to exceed in physical effort and maintain optimal health.[13]

All patients diagnosed with hyperlipidemia must understand how the disease affects their organs and the health risks that it may pose. A proper diet, smoking cessation, and lifestyle modifications should always be discussed. If pharmacological therapy is necessary, discussion of the risks and benefits of each medication should be explored before initiation. The primary care physician and pharmacist alike have a duty to educate the patient on medication compliance, side effects, interactions, and the overall risks versus benefits of the medications prescribed. The patient must also understand the potential risks related to not taking the medication and what alternatives they may have as treatment options.

The diagnosis of hyperlipidemia can be a difficult one, often in the sense that there are no presenting symptoms. To establish a diagnosis, the primary care physician or attending physician ordering lab work must have a high suspicion for the disease or be completing routine screening labs. Typically the physician needs collaboration with nurses (obtain vital signs, asking history, etc.) who are also critical in the overall process of good patient care. Once the diagnosis is made, interprofessional communication and teamwork are vital to ensure the patient receives proper treatment based on the most up to date treatment guidelines.

Following diagnosis, the primary care physician typically will manage the disorder with diet, exercise, and/or medications. This diagnosis and treatment plan must be communicated to the patient's other physicians for optimal care. It also involves communication with the patient about medication side effects from the prescribing doctor and also from the pharmacist if needed. The pharmacist is also able to re-explain any potential adverse effects or interactions from the medications prescribed by the physician.

If diet education is needed, often, the patient can consult with a nutritionist or dietitian.

Proper interprofessional communication between these specialties and subspecialties and with the patient will ensure correct treatment and medication adherence, keeping the patient safe, and ideally preventing the progression of the disease. The patient should be monitored yearly or more often at the discretion of his or her primary care physician to keep close tabs on the progression of the disease.