We typically think of inflammation occurring suddenly after an injury or an infection — such as a red, swollen joint — a process in which the body releases chemicals and infection-fighting white blood immune cells to aide in the body’s healing process. But did you know that inflammation can also be a long-term problem? It can be a “slow burn,” where the body releases low levels of these same blood chemicals, often in response to being overweight, not being physically active or having too-high levels of blood sugar in the form of glucose. Although it is not proven yet that inflammation directly causes cardiovascular diseases, we know that chronic, low-grade inflammation is closely linked to all stages of atherosclerosis, a disease that underlies heart attack, stroke and peripheral artery disease.
Atherosclerosis describes the cholesterol layers, or plaques, that are often found along the inside of our blood vessels, especially as we get older. Coronary artery disease refers to atherosclerosis of the blood vessels that supply blood to the heart muscle, but it can also affect other arteries in the body, such as those that supply blood to the brain, legs, arms and gut. The inciting event in atherosclerosis development is the movement of low-density lipoprotein (LDL) cholesterol, known as “bad” cholesterol, into the innermost layer of the vessel wall, though it is not quite clear what triggers this. LDL cholesterol is quickly followed by white blood cells and thus begins the process of plaque formation, consisting mainly of cholesterol, fatty substances and waste products of cells. As this process continues, the walls of the blood vessels become more and more inflamed and irritated, resulting in continuous damage and growth of these plaques.
The formation of atherosclerotic plaques can take decades, though it may start as early as childhood. As they grow in size, they start to narrow the artery, much like a blocked pipe. As a result, blood flow and oxygen delivery to the heart muscle are reduced, which can be a cause of cardiac chest pain (angina). Plaques can be either stable or unstable, and it is these unstable (or vulnerable) plaques that are more likely to cause trouble in the future.
Atherosclerotic plaques in the arteries are covered with a layer of tissue called a fibrous cap. The initial event that leads to a heart attack is thought to be rupture or erosion of this protective cap. When this layer of cells is damaged, the underlying chemical components of the inflamed plaque become exposed to the bloodstream, causing the body to overreact and trigger the formation of a blood clot inside of the artery. This leads to a partial or complete obstruction of blood flow to the heart muscle, causing heart damage. The sequence of events that leads to this plaque rupture is not completely understood, though chronic inflammation of the artery walls is thought to play an important role and make certain plaques more vulnerable to rupturing.
[See: The Best Foods for Lowering Your Blood Pressure.]
C-Reactive Protein: A Blood Test of Inflammation
One of the most extensively studied markers of inflammation in the body is C-reactive protein, which is a protein made by the liver. C-reactive protein levels increase in infection, cancer, obesity and diabetes; in smokers; and in response to certain drugs, like hormone replacement therapy. It is also found to be elevated, though to a lesser extent, in patients with or at risk for cardiovascular disease.
We can test for low levels of this protein in the blood using a very sensitive test called the high-sensitivity C-reactive protein, or hsCRP, test. There is no definitive threshold of hsCRP levels for identifying those who are at increased risk of heart disease, so the Centers for Disease Control and Prevention and the American Heart Association have provided guidelines on how to test hsCRP levels and what levels may identify people at higher risk.
— Results used should be an average of two hsCRP tests, two or more weeks apart.
— Low risk is defined as less than 1 milligram per liter, average risk as 1 to 3 milligrams per liter and high risk as greater than 3 milligrams per liter.
— Levels greater than 10 milligrams per liter should prompt investigation for infection or inflammatory health conditions.
C-Reactive Protein: A Marker of Cardiovascular Disease Risk
There are several well-established and proven risk factors for coronary heart disease, such as high blood pressure, high cholesterol, diabetes, smoking and family history of early heart disease. The hsCRP level is not part of this list, though an elevated hsCRP level has been shown to predict the long-term risk of a first heart attack or stroke, high blood pressure development, vascular disease and sudden cardiac death.
In the PEACE clinical trial, researchers showed that men or women with a history of coronary heart disease and with a hsCRP level greater than or equal to 1 milligram per liter had a somewhat higher rate of cardiovascular death, heart attack or stroke when compared to those with a level less than 1 milligram per liter. However, measuring hsCRP levels is even more useful for those without a history of heart disease to help identify people at risk. In the Women’s Health Study of nearly 28,000 apparently healthy women, hsCRP testing helped identify women at increased cardiovascular risk, providing additional information about their heart disease prognosis compared to predicting cardiovascular risk using traditional risk factors alone.
However, whether hsCRP levels increase as a result of underlying heart disease risk factors or whether these high levels of hsCRP directly stimulates disease progression is not clear. Either way, some studies have shown that with reduction in hsCRP levels, there is an observed improvement in outcomes.
[See: The 12 Best Diets for Your Heart.]
C-Reactive Protein, LDL-Cholesterol and Statin Therapy: What the Research Says
The good news is that losing weight, particularly around the abdomen, and exercising can reduce inflammation in the body, which is reflected by lower hsCRP levels. We also know that a class of medications called statins, which lower cholesterol, can also lower hsCRP levels, but it is debatable whether that is due to the cholesterol reduction or to another cause.
The JUPITER clinical trial evaluated whether statins could reduce heart attacks and strokes in people with normal cholesterol levels but who had evidence of inflammation. It involved 17,802 healthy men over 50 and women over 60 with a “normal” LDL cholesterol level — less than 130 milligrams per deciliter — and an elevated hsCRP level — greater than or equal to 2 milligrams per liter. Patients were treated with either 20 milligrams of the statin rosuvastatin or placebo. Rosuvastatin treatment reduced LDL cholesterol levels by 50 percent and hsCRP levels by 37 percent, and this translated to an impressive 44 percent relative reduction of heart attack, stroke or death rates after an average follow-up of two years.
Another clinical study, the IMPROVE-IT trial, involved 18,144 patients who were treated with the statin simvastatin or simvastatin plus the cholesterol-lowering drug ezetimibe. The study showed a greater reduction in both LDL cholesterol and hsCRP with the combination of drugs. The group who achieved both a low LDL cholesterol level of less than 70 milligrams per deciliter and a low hsCRP level of less than 2 milligrams per liter had a 27 percent reduction in rate of cardiovascular death, heart attack or stroke.
Altogether, these trials show us that statin medications can lower both LDL cholesterol and hsCRP, and that patients with lower levels of both blood markers have the best outcomes. So, from these trials, we can see that a lower hsCRP level appears to be something we should all strive for.
Who Should Be Screened Using hsCRP Testing?
The 2013 American College of Cardiology and American Heart Association guidelines on the assessment of cardiovascular risk use a newly developed tool, the atherosclerotic cardiovascular disease (ASCVD) risk score, which helps the clinician and the patient estimate the risk of a first heart attack or stroke within 10 years. The risk assessment tool provides a sex- and race-specific estimate of the 10-year risk of a first heart attack or stroke in African-American and white men and women ages 40 to 79.
With this tool, patients are assigned a percentage risk estimate, which helps to determine whether or not the patient would benefit from starting a statin drug to lower their cardiovascular disease risk. For patients who fall into a very high-risk category (recommended to start a statin) or a very low-risk category (recommended for lifestyle changes only), the answer is easy. However, for many patients, their risk for cardiovascular disease remains uncertain after using this tool; this is where hsCRP level can be useful. The experts recommend that, if there is still uncertainty as to whether drug therapy should be initiated after the formal risk assessment, the results of the hsCRP test may help guide that decision. If the level is greater than or equal to 2 milligrams per liter, this would support revising the risk assessment to a higher-risk category. In other words, if your risk for cardiovascular disease is still uncertain after measuring the traditional risk factors and your hsCRP level is greater than or equal to 2 milligrams per liter, then you may benefit from a statin. Statins can reduce hsCRP levels after only two weeks of therapy.
[See: Exercising After You’ve Gone Under (the Knife, That Is).]
What Can You Do?
Despite all of the focus on statin therapy in helping to prevent heart disease, lifestyle modification should still be the foundation for cardiovascular disease prevention. The American Heart Association dietary guidelines focus on a wide and varied diet rich in fruit, vegetables and whole grains, and low in salt, added sugar and saturated fats. The aim is to reduce the high levels of diabetes, obesity, high blood pressure and heart disease — all associated with increased inflammation in the body — in the American population by getting to the root of the problem. Additionally, low saturated fat diets have been shown to help reduce hsCRP levels by up to 10 percent, which is further improved to 33 percent when statin therapy is added. High-fiber, low-carbohydrate eating patterns are also beneficial in reducing hsCRP. Essentially, by losing weight, increasing exercise and improving blood pressure and cholesterol levels, we can lower our risk of heart disease quite significantly.
Lastly, if you are worried about your future risk of heart disease or stroke, ask your doctor to perform your ASCVD risk score. If your cardiovascular risk is uncertain after your other risk factors have been checked, hsCRP testing or a scan may help to decide whether or not a statin is the right choice for you. And know that everyone from all risk groups can benefit from a heart-healthy lifestyle to keep their inflammation in check.
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Inflammation and Heart Disease: What Is C-Reactive Protein? Who Might Benefit from Testing? originally appeared on usnews.com
