Hypercholesterolemia: Clinical practice

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Hypercholesterolemia: Clinical practice

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A 65-year-old man comes to the office because of pain in the lower extremities. The pain is associated with walking and relieved by rest. He has a history of myocardial infarction, hypertension, hyperlipidemia, diabetes mellitus, and smoking. Examination of the legs shows atrophic changes with diminished pedal pulses. Which of the following is the most appropriate initial treatment? 

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Content Reviewers:

Rishi Desai, MD, MPH

Cholesterol is a lipid molecule that helps maintain the structure of cell membranes, and is a precursor to steroid hormones, bile acids, and vitamin D.

Although, every day, some new cholesterol comes in through the diet, most of the cholesterol we need is obtained through recycling existing cholesterol.

Most of that recycling happens in the intestines and is facilitated by bile acids which help us reabsorb cholesterol and bring it back into the bloodstream.

There are two main types of cholesterol: HDL or High Density Lipoprotein which is sometimes called “good cholesterol”, and LDL or Low Density Lipoprotein which is sometimes called “bad cholesterol”. But good and bad is overly simplistic, and like all things - the subtleties matter.

LDL is produced by the liver and it carries cholesterol out to the rest of the body.

If all of the cholesterol from LDL is not completely distributed to the peripheral cells, then HDL brings some of that cholesterol back from the peripheral tissues and sends it to the liver.

Now, what makes LDL bad and HDL good is that, whenever there’s a high blood concentration of LDL, the LDL can be ingested by macrophages that sit along vessel walls, forming atherosclerotic plaques.

Over decades, large atherosclerotic plaques can lead to myocardial infarctions, strokes, and peripheral vascular disease. That’s why we want to keep LDL blood levels under control.

On the other hand, HDL can remove cholesterol from cells and that can help reverse the process of atherosclerosis.

A diagnosis of hypercholesterolemia requires measuring total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides.

Cholesterol is measured either as milligrams per deciliter (mg/dL) or millimoles per liter of blood (mmol/L), and it’s recommended to test cholesterol every five years for people aged 20 years or older.

Hypercholesterolemia is defined as having cholesterol levels that predict a higher risk of atherosclerosis and cardiovascular disease.

The total blood cholesterol is the total amount of cholesterol in your blood, and it includes the LDL, HDL, and VLDL, and it should be below 200 mg/dL or 5.2 mmol/L.

The HDL level should be above 60 mg/dL or 1.55 mmol/L, and the LDL level should be below 130 mg/dL or 3.3 mmol/L in most individuals, or below 70 mg/dL or 1.8 mmol/L in people who have previously had a cardiovascular event.

And of the three - total cholesterol, LDL, and HDL - the LDL is the most relevant indicator of risk.

Finally, triglycerides are also often measured along with cholesterol because elevated triglycerides can contribute to atherosclerosis.

And having elevated triglycerides is specifically termed hypertriglyceridemia, rather than hypercholesterolemia.

Now, first off, individuals with hypercholesterolemia should make lifestyle modifications, such as exercise and weight loss to achieve a healthy BMI between 18.5 and 25, avoid cigarettes and tobacco products, and reduce consumption of saturated fats, so eating fewer animal products like meat and dairy.

Usually, individuals with a very elevated LDL or with a combination of a moderately elevated LDL and other risk factors for cardiovascular disease are prescribed lipid-lowering medications.

Common risk factors for cardiovascular disease include being a man over the age of 45 or a woman over the age of 50 with HDL cholesterol less than 40 mg/dL or 1 mmol/L, having diabetes, hypertension, a family history of coronary artery disease and hypercholesterolemia, and cigarette smoking.

To be more specific, individuals with an LDL above 190 mg/dL or 4.9 mmol/L, or those with an LDL above 160 mg/dL or 4.1 mmol/L with two or more additional risk factors are started on medication.

Treatment is also started in individuals with an LDL above 130 mg/dL or 3.4 mmol/L with asymptomatic coronary artery disease, as well as individuals above 70 mg/dL or 1.8 mmol/L who have previously had a cardiovascular event.

Now, there are five main classes of lipid-lowering medications: statins, selective cholesterol absorption inhibitors like ezetimibe, fibrates, bile acid sequestrants, and niacin.

The first option are statins and they’re generally the first choice in most situations - they lower LDL and triglycerides, and mildly raise the HDL.

In patients that have never had a cardiovascular event, a low to moderate dose of a statin is used - like 10 to 20 mg of atorvastatin or 5 to 10 mg of rosuvastatin.

LDL is usually measured six weeks after starting statin therapy to see if there’s a response and then done every 6 to 12 months thereafter.

The goal is to get the LDL below 100 mg/dL or 2.6 mmol/L.

If the LDL remains above that level, then one option is to gradually increase the statin dose up to 40 to 80 mg of atorvastatin or 20 to 40 mg of rosuvastatin.

On the other hand, for patients with a previous cardiovascular event, lifelong high dose statin therapy with 40 to 80 mg of atorvastatin or 20 to 40 mg of rosuvastatin is used regardless of baseline LDL levels.