High Cholesterol

Why does high cholesterol matter and what’s the connection with heart disease?

Cardiovascular (heart) disease is the leading cause of death in the world. It's a complex process, but one of the major risk factors is high cholesterol or, more specifically, elevated levels of atherogenic “lipoproteins,” cholesterol-containing molecules that contribute to atherosclerosis (the buildup of fats, cholesterol, and other substances within blood vessel walls).

What are high cholesterol symptoms?

High cholesterol has no symptoms, but a simple blood test can detect this risk factor for heart disease.

What is meant by LDL and HDL and why do they matter?

Cholesterol is not water-soluble, so it needs to be packaged with a protein transporter, a “lipoprotein,” to move through the blood. These lipoproteins are categorized by their density.

Low-density lipoprotein (LDL) particles transport cholesterol from the liver to the different tissues of the body. Unfortunately, the LDL particles can also deposit cholesterol within the vessel wall, starting the process of atherosclerosis.

High-density lipoprotein (HDL) particles, on the other hand, transport cholesterol from different tissues back to the liver for processing or excretion. This includes harvesting cholesterol deposited within the vessel wall by the LDL, decreasing its cholesterol burden.

How does cholesterol contribute to cardiovascular disease?

Cholesterol deposited within the walls of blood vessels can trigger an inflammatory cascade leading to plaque formation, an early step in cardiovascular disease. The relationship between plaque progression and symptomatic disease is multifactorial.

Studies show a more rapid progression to clinical cardiovascular disease (heart attack, angina, sudden cardiac death, stroke) in patients with a greater number of risk factors such as advanced age, smoking, diabetes, high blood pressure, and elevated cholesterol.

What other factors matter when considering whether or not a person’s cholesterol puts them at higher risk for disease?

Other factors that contribute to an increased risk of cardiovascular disease are advanced age, high blood pressure, diabetes, metabolic syndrome, family history of heart disease, other inflammatory diseases, elevated high sensitivity c-reactive protein (hs-CRP), ethnicity, and kidney disease.

Can you talk about “residual risk” and why this is such an important concept in understanding cholesterol treatment?

Imagine you’re treating someone at high risk for cardiovascular disease, and you put them on a statin (a class of medication commonly used for high cholesterol). You’ve likely decreased their risk of having a heart attack by 25-30% (compared to their elevated baseline risk), but they still have a higher risk compared to average, or what we call “residual risk.” So why doesn’t the statin decrease the risk to baseline?

First, we’re addressing the disease too late in the process, and there are vessels that are damaged beyond repair. (Cardiovascular disease can start in people’s 20s, so if we only begin to address it in people’s 50s, we may not be able to influence the disease process as much as we’d like.)

Second, we’re looking at only a small part of the big picture. We’re treating cholesterol, which may only be one part of a more complex disease process.

What about HDL, “good cholesterol”?

Previously, experts believed that elevated HDL cholesterol levels were always beneficial. Recent studies, however, showed that increasing these levels with medication did not decrease cardiovascular disease in patients, suggesting that the ability of HDL particles to transport cholesterol was more important than the number alone. Unfortunately, we don’t have a way to measure this function yet.