As we grow older, we become more and more likely to develop heart disease. Obviously, we don’t think about it much in our twenties and thirties unless we’ve seen a close family member or a friend being hit by a heart attack or stroke. But, ultimately, most of realize that we should care.
Since cardiovascular disease is to a certain extent preventable, we should be eager to learn how we can modify our risk and at least do our best to delay the onset of these disorders.
One way to assess risk is to have our blood lipids measured. Knowing our cholesterol level is considered valuable and lowering it is usually recommended. But how about other types of fats in our blood stream? What about triglycerides, do they matter?
Interestingly, when it comes to assessing the risk of cardiovascular disease, triglycerides have always played second fiddle to cholesterol.
As a result, dietary advice for people with heart disease usually aims at lowering blood cholesterol, particularly LDL cholesterol. Therefore, replacing saturated fat with polyunsaturated and monounsaturated fats, and increasing the intake of food products rich in fiber and complex carbohydrates such as whole grains, is usually recommended.
Furthermore, statin drugs play a key role in the treatment of people with coronary heart disease, mostly because they lower LDL cholesterol.
One of the reasons it’s complicated to address triglycerides at the same time as LDL cholesterol is that a diet that lowers LDL cholesterol may raise triglycerides and vice versa. For example, low-fat diets may lower LDL cholesterol but are less effective in lowering triglycerides compared to low-carbohydrate diets (1).
Another reason we’ve tended to ignore triglycerides is that the pharmaceutical industry has shown limited interest in developing drugs that influence triglycerides.
However, recent genetic studies suggest that triglycerides do play a causative role in cardiovascular disease.
Furthermore, a recent paper published in the Journal of the American College of Cardiology suggests that among patients with acute coronary syndrome treated effectively with statins, fasting triglycerides predict long-term and short-term cardiovascular risk (2).
Before we dig deeper into the role of triglycerides in heart disease, let me take you on a short journey to help you understand the role of triglyceride-rich lipoproteins.
If you’re not in the mood for the biochemistry, just skip to the next chapter.
The Role of Triglyceride Rich Lipoproteins
Just like other types of fats, triglycerides are carried in the bloodstream by lipoproteins. Chylomicron and VLDL (very low-density lipoprotein) er examples of triglyceride-rich lipoproteins.
Chylomicron and VLDL remnants contribute to the building of plaques in our arteries (atherosclerosis) and are therefore considered atherogenic.
The fats we consume in our diet are mainly composed of triglycerides. Therefore, following a fatty meal, blood levels of triglycerides will rise.
It is important to understand that raised blood triglycerides following a meal (postprandial hypertriglyceridemia) are caused by chylomicrons while elevated fasting levels are due to high VLDL, often caused by excessive carbohydrate intake. Both these types of hypertriglyceridemia may contribute to atherosclerosis.
Chylomicrons are formed in the intestine after a meal. They contain triglycerides and small amounts of cholesterol. They are initially exported to intestinal lymph nodes and after that reach the circulation where they may contribute to postprandial hypertriglyceridemia.
An enzyme called lipoprotein lipase subsequently breaks down chylomicrons into free fatty acids that are used as fuel by the heart and skeletal muscles or stored in adipose (fat) tissue.
Chylomicron remnants are removed from the circulation, partly through the LDL-receptor.
VLDL is synthesized by the liver. It contains both triglycerides and cholesterol.
Once in circulation, VLDL comes in contact with lipoprotein lipase in the capillary beds. Lipoprotein lipase catalyzes the breakdown of VLDL, releasing triglycerides for energy production or storage in adipose tissue.
After the removal of triglycerides from VLDL, the composition of the lipoprotein changes and it becomes intermediate-density lipoprotein (IDL). Later, when the amount of cholesterol increases, IDL becomes low-density lipoprotein (LDL). These LDL particles are typically small. Small LDL particles are associated with increased risk of cardiovascular events (3).
Both chylomicrons and VLDL promote inflammation.
High levels of chylomicrons increase the risk of acute pancreatitis, an inflammation of the pancreas. Chylomicron and VLDL remnants increase inflammation of the endothelium (the innermost layer of the artery).
Triglyceride rich lipoproteins increase atherosclerosis, inflammation and the lipid content of arterial plaques (4).
VLDL Cholesterol and Atherosclerosis
Non-HDL cholesterol is a measure of the cholesterol content transported in all atherogenic lipoproteins. It is calculated by subtracting HDL cholesterol from the total cholesterol. Non-HDL cholesterol is a greater predictor of cardiovascular risk than LDL cholesterol.
High triglycerides are usually accompanied by elevated levels of non-HDL cholesterol, small LDL particle size, and high LDL particle concentration.
VLDL cholesterol can be calculated by subtracting directly measured LDL cholesterol from non-HDL cholesterol. Recent data suggests that VLDL cholesterol or remnant cholesterol is a stronger promoter of atherosclerosis than LDL cholesterol (5).
Chylomicron remnants and VLDL remnants have been shown to rapidly penetrate the arterial wall and promote atherosclerosis (6).
Triglycerides and Coronary Heart Disease
Despite evidence that chylomicron and VLDL remnants promote atherosclerosis, the importance of lowering triglycerides has not been considered a priority for patients with coronary heart disease.
Recent genetic studies have addressed the relationship between triglyceride-rich lipoproteins and the risk of cardiovascular events. The results of one of these studies imply that the elevated cholesterol content of triglyceride-rich lipoprotein particles may cause coronary heart disease (7). Another study found that a genetic mutation associated with low blood levels of triglycerides was associated with less risk of cardiovascular disease (8).
These studies strongly support the hypothesis that high blood levels of triglycerides may increase the risk of cardiovascular disease and that low levels may be protective.
But what about people with established coronary heart disease? Do triglycerides matter for them?
Acute Coronary Syndrome
Acute coronary syndrome is an umbrella term for situations where the blood flow to the heart muscle is suddenly blocked.
It is most often caused by a plaque in a coronary artery with a superimposed blood clot (thrombosis). The blockage may be sudden or intermittent. Acute heart attack and unstable angina are both examples of acute coronary syndromes.
Acute coronary syndrome is a medical emergency calling for hospital admission. There is a risk of damage to the heart muscle and arrhythmia, sometimes leading to cardiac arrest.
Treatment aims at restoring normal blood flow in the blocked vessel and prevent recurrent events.
Although the mortality from coronary heart disease has declined, patients with acute coronary syndrome face a high risk of having recurrent events, despite intensive statin therapy and blood thinning treatment. This is called residual risk.
Reducing residual risk is the main target of therapy following an acute coronary event. It can be accomplished by lifestyle modification and drug treatment.
If prognosis is to be improved, it is important to define the factors that contribute to residual risk.
Acute Coronary Syndrome, Triglycerides, and Residual Risk
Statins effectively lower LDL cholesterol and reduce blood levels of triglyceride-rich lipoproteins. However, although target levels of LDL cholesterol may be achieved by statin treatment, triglycerides may remain high and triglyceride-rich lipoproteins may be a target for further therapy
Recently, investigators from Denver, Colorado addressed the relationship between fasting triglycerides and cardiovascular risk after acute coronary syndrome in two large trials (dal-OUTCOMES and MIRACL) of patients treated with statins (2).
The results show that fasting triglyceride levels are associated with both short-term (16 weeks) and long-term (3.5 years) risk after ACS. Adjustment for age, sex, hypertension, current smoking, diabetes, HDL cholesterol and body mass index did not affect the relationship.
The authors conclude that despite a background of intensive statin therapy, there was a strong, unfavorable relationship of fasting triglyceride levels to short-term and long-term prognosis after acute coronary syndrome. They believe their findings show that triglyceride-rich lipoproteins may have a causal relationship to risk after acute coronary syndrome.
Furthermore, it is concluded that non-HDL cholesterol may be the best long-term risk indicator because it reflects the cholesterol content of both LDL- and triglyceride-rich lipoproteins.
Lifestyle Modification and Triglycerides
If triglycerides play a causative role in coronary heart disease, lowering them appears a reasonable target.
Raised levels of triglycerides are commonly associated with obesity and the metabolic syndrome. Furthermore, elevated triglycerides are often associated with low HDL cholesterol. The triglyceride/HDL cholesterol ratio is a strong predictor of risk.
In those who are overweight, losing weight will likely lower triglyceride levels and so will reducing the intake of added sugar. Studies have shown that the intake of fructose and high-fructose corn syrup increases triglycerides (11).
Low-fat, high-carb diets may be problematic because they often raise triglyceride levels (12). In controlled trials, low-carb diets lower triglycerides more than low-fat diets.
Adding omega-3 fatty acids, regular physical exercise and limiting alcohol may help to lower triglycerides.
The Take-Home Message
There is substantial evidence that triglyceride-rich lipoproteins may play a causative role in atherosclerosis and coronary heart disease.
Recent studies suggest that among patients with coronary artery disease who are on intensive statin treatment and have optimal levels of LDL cholesterol, triglyceride levels remain a significant predictor of residual risk.
Evidence suggests that low-carb diets may lower triglyceride more effectively than low-fat diets.
Dietary and lifestyle recommendations to reduce the risk of cardiovascular disease may have to be reevaluated and to a greater extent targeted at lowering triglyceride-rich lipoproteins.