What Is the Connection Between Cholesterol and Inflammation in Heart Disease?

So, what actually is cholesterol, and why does it have such a significant impact on our cardiovascular health? Here's what you should know about the relationship between cholesterol and inflammation. 

Cholesterol has long been seen as a key culprit in cardiovascular disease—an umbrella term for the conditions that affect the heart and blood vessels. But in addition to cholesterol, many other factors contribute to the development of heart diseases, such as blood pressure, blood sugar, and weight.

What Is Cholesterol?

Cholesterol is a waxy, fatty substance produced by the liver but also occurs in foods. It comes in two main types: Low-density lipoprotein (LDL), or "bad" cholesterol, and high-density lipoprotein (HDL), or "good" cholesterol. 

Cholesterol in the blood is essential for maintaining good health because it performs vital functions, like making hormones and breaking down fatty foods.

But too much cholesterol can be a bad thing. That's because high LDL cholesterol levels—combined with low HDL cholesterol levels—put people at risk of cardiovascular diseases like coronary heart disease, heart attack, and stroke.

Measuring Cholesterol

To measure cholesterol levels, your healthcare provider will have you take a blood test called a lipoprotein panel (or lipid panel). Before you take the test, you need to fast for nine to 12 hours (you can have only water, no food or other beverages). 

The lipoprotein panel will measure your total, LDL, HDL, and non-HDL cholesterol. It will also measure your triglycerides, another type of fat in your blood that can increase your chances of developing heart disease.

For adults, measured in milligrams per decilitre, healthy levels are:

  • Total cholesterol: 125 to 200 
  • LDL cholesterol: Less than 100 
  • HDL cholesterol: 50 or higher and 40 or higher for cisgender women and men, respectively 
  • Non-HDL cholesterol: Less than 130  
  • Triglycerides: Less than 150 

Regarding when you should receive the test, there are different recommendations. Starting at about 10 years, you should receive the test every five years. For cisgender men and women, people aged 45 to 65 years or 55 to 65 years, respectively, should receive the test every one to two years. However, people with high-risk factors and a family history of high cholesterol or cardiovascular disease should receive the test more often.

What About Inflammation?

Research has identified inflammation as a primary source of chronic diseases like heart disease.

Inflammation is the flood of white blood cells and chemicals our immune system unleashes to ward off damage or infection. Cholesterol wouldn't be nearly as dangerous without that process, which is essential in atherosclerosis. Atherosclerosis is the hardening of the arteries that occurs when LDL cholesterol builds up.

When high cholesterol levels occur in the bloodstream, excess LDL cholesterol begins to seep into the artery's inner wall. That triggers an inflammatory response, which speeds up cholesterol accumulation in the artery wall.

And that, in turn, produces more inflammation—and on and on. Eventually, the deposited cholesterol hardens into a plaque, which can rupture and lead to blood clots that cause heart attacks and strokes.

What's more, some experts now believe that inflammation links to many diseases and conditions that affect the heart and brain. 

"Inflammation is the common denominator in nearly all of the diseases we deal with," said James H. O'Keefe, MD, a cardiologist and medical director of the Charles and Barbara Duboc Cardio Health & Wellness Center at Saint Luke’s Mid America Heart Institute in Kansas City, Mo. "Heart disease, diabetes, dementia. They're all tied to inappropriate, low-grade, chronic inflammation."

Measuring Inflammation

Our growing understanding of inflammation's role in atherosclerosis doesn't diminish the importance of cholesterol. You still have to keep your LDL cholesterol level low and your HDL cholesterol level high. But it does present another way to anticipate heart disease.

A substance known as C-reactive protein (CRP) is one of the markers released by cells in the liver in response to inflammation. CRP may be more effective than cholesterol in gauging the risk of heart attack and other cardiovascular events. 

In fact, some research has shown that CRP is "the most clinically useful" biological marker of atherosclerosis. Other studies have confirmed CRP's predictive role in developing cardiovascular disease and several other inflammation-related conditions.

In 1999, the Food and Drug Administration approved a CRP test specifically designed to measure the risk for cardiovascular disease, known as a high-sensitivity C-reactive protein (hsCRP) assay. And the test became nearly as routine as the lipoprotein panel. Some healthcare providers even administer the hsCRP test, which requires a simple blood workup, as part of annual physical exams.

Still, the importance of CRP is a matter of dispute.

"One of the issues and controversies regarding CRP as a risk factor for cardiovascular disease has been whether it is simply a marker or whether the higher levels actually cause heart attack and stroke," explained Alexander Reiner, MD, a research professor of epidemiology at the University of Washington School of Public Health in Seattle. "It's very difficult to tease that out. It can work both ways, and my guess is, it probably does." 

CRP levels may be modifiable through lifestyle adjustments. Research has found that lifestyle adjustments decrease CRP levels by stopping smoking, increasing physical activity, eating healthy, and losing weight.

Dr. Reiner is among a group of researchers across the United States who look at genes to establish a link between inflammatory markers and the risk of cardiovascular events. 

Those researchers identify genetic variations that predict CRP levels and variations that predict heart attacks and other events. But they have yet to find a single gene that indicates both. That gene would prove the connection between CRP and cardiovascular disease if it exists. 

"That would be the holy grail," said Dr. Reiner.

Implications for Treatment

So, the exact role of inflammatory markers is unclear. But if your CRP test uncovers high levels of CRP (over three milligrams per liter), you should assess your cardiovascular disease risk. That's even if you have normal cholesterol. For instance, your healthcare provider may start you on aspirin therapy or, more likely, a cholesterol-lowering medication.

Research has shown that those medications, also called statins, reduce inflammation and lower the levels of inflammatory markers, including CRP. Even though some statins have more potent effects on inflammation than others, they are still effective treatments for inflammation.

While people frequently use statins, other studies have found additional medications, like colchicine, that may reduce inflammation and CRP levels.

But medications aren't a silver bullet. As with cholesterol, you should manage inflammation by maintaining a healthy weight, exercising, quitting smoking, and following a healthy diet.

Specifically, a poor diet can aggravate inflammation. High-calorie and high-fat meals may cause a sudden spike in CRP and other inflammatory markers.

"The inflammation is due to a fundamental problem of using the wrong fuel for the engine," explained Dr. O'Keefe. "We're not designed to burn this stuff. And when we do, it throws off all these inflammatory by-products." 

To keep inflammation to a minimum, Dr. O'Keefe recommended a restricted-calorie diet (similar to the Mediterranean diet). That diet consists of fruits and vegetables, lean protein, nuts, vinegar, tea, and fish oil, as well as low to moderate alcohol intake.

"The key to restoring good health to America is getting people to tune in to the connection between the dynamic, hour-to-hour nature of inflammation and their general health and well-being—of their heart, their brain, their blood," noted Dr. O'Keefe. "From a health standpoint, nothing is more important than keeping those inflammation levels down."

Summary

Not everyone is convinced that inflammation is the next big thing in cardiac care. Supporters of the inflammation theory admit that it is unlikely to become more important than cholesterol. Thus, researchers continue to investigate the role of inflammation and the value of CRP.

At the same time, they may prove helpful to test and treat. Still, those markers will not take the place of cholesterol any time soon, said Alan Daugherty, PhD, DSc, FAHA, director of the Saha Cardiovascular Research Center at the University of Kentucky College of Medicine in Lexington, Ky.

"If you gave physicians a choice between doing a test for cholesterol or CRP," said Dr. Daugherty, "I'm fairly certain that more than 90% would take the LDL cholesterol measurement." 

Treatment for inflammation, added Dr. Daugherty, will continue to take a backseat to cholesterol-based treatments for the foreseeable future. 

"I very much doubt it will ever be a substitute for cholesterol-lowering, but it might very well be an add-on," noted Dr. Daugherty.

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Sources
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