Coronary heart disease is responsible for one out of every four deaths per year, according to the Centers for Disease Control and Prevention. Doctors associate elevated low-density lipoproteins (lousy LDL cholesterol) with coronary artery disease, the leading cause of death in the United States. But what about the other lipids or fats circulating in the blood?
Two years ago, Dr. Sekar Kathiresan, a Broad Institute associate member and director of preventive cardiology at Massachusetts General Hospital, and his colleagues led a large-scale genetic study that found no causal association between high-density lipoproteins (healthy HDL cholesterol) and heart disease. These findings challenged the long-held view that increasing good HDL levels lowers heart disease risk.
Then a study published in Nature Genetics last year uncovered an association between triglycerides, the most common type of fat in the body, and coronary artery disease that suggested a causal link. So Kathiresan and other Broad Institute researchers harnessed genomic methods to explore the connection between triglycerides and heart disease. By assessing the role of rare genetic variants through DNA sequencing, they hoped to pinpoint specific genes that affect both triglyceride levels and heart disease risk.
Altered APOC3 Gene Discovery Improves Blood Tests
Your liver makes the APOC3 protein and pours it out into your blood stream. Scientists believe it prevents the removal of triglyceride-rich lipoproteins from your blood, especially by delaying clearance after meals. Kathiresan and his research team sequenced exomes, the one percent of genomes that carries protein-forming information, in almost 3,800 subjects. According to the study published in the New England Journal of Medicine, they identified four rare mutations in the APOC3 gene that lower triglyceride levels significantly.
Researchers found at least one APOC3 gene aberration in one out of 150 study participants. Subjects carrying a single mutation had about 40 percent lower triglyceride levels. Normal levels are less than 150 milligrams per deciliter (mg/dL), and high triglyceride levels are greater than 200 mg/dL. But with APOC3 mutations, participants’ triglyceride levels were around 85 mg/dL. In addition, good HDL cholesterol levels were 22 percent higher in people with mutations, and their bad LDL cholesterol levels were 16 percent lower than those in the control group.
The researchers believe the gene variations cleared triglyceride-rich lipoproteins faster so less enter the blood and damage coronary artery walls. These findings suggest that high triglyceride levels — not low levels of good HDL cholesterol — play a major role in contributing to heart disease.
Establishing the Heart Protection Bonus
HDL and triglycerides have an inverse relationship. The lower the HDL, the higher the triglycerides. Kathiresan noted that doctors have presumed for some time that low HDL is the causal factor of heart disease with triglycerides going along for the ride. But this new genetic data sheds light on the biological role of triglycerides as the true culprit.
To establish a definitive relationship between these mutations and coronary heart disease risk — specifically heart attack incidence — Kathiresan’s researcher team analyzed over 110,000 patient samples. They genotyped the relevant parts of the APOC3 gene and compared heart attack rates in people carrying mutations to those without them. DNA analysis discovered that these anomalies reduced coronary heart disease risk by 40 percent in carriers.
Study senior co-author Dr. Alex Reiner, a member of the Public Health Sciences Division at Fred Hutchinson Cancer Research Center and a research professor of epidemiology at the University of Washington’s School of Public Health, indicated that preventive measures might need revision. The research team advises that lowering triglycerides is the way to reduce heart disease risk.
Additional Studies Support Positive Results
A small 2008 heart disease study found one of these APOC3 aberrations in the Lancaster Amish community. That research also discovered an association with lower triglyceride levels. Carriers had less calcium in their coronary arteries, a sign of limited accumulating fat, which suggested that the mutation protected against heart disease.
Another study from Denmark researchers at the University of Copenhagen examined the APOC3 gene in 75,725 people and followed them for 34 years. The investigators found those with mutations had 44 percent lower triglyceride levels and 36 percent lower heart attack risks.
Future Treatments Are on the Horizon
These studies represent a breakthrough in research for heart disease prevention. Their findings could lead to the development of a new generation of drugs that target the APOC3 gene. Turning off its unhealthy function can do more than lower elevated triglyceride levels. It can prevent heart disease, which will avert cardiac arrest and stroke among high-risk people.
Benefit from Fish Oil Today
Current triglyceride-lowering medications include fish-oil-based Omacor. It consists of a high concentration of eicosapentaenoic acid and docosahexanoic acid, two highly purified Omega-3 fatty acid ethyl esters. You may take this drug alone or in combination with other cholesterol-lowering medications. Your doctor should do regular blood tests to check your triglyceride and cholesterol levels, adjusting your dosage as necessary.
Other Ways to Lower Your Triglycerides
Be physically active, maintain a healthy weight and don’t smoke. Eating a low-fat, low-cholesterol diet can help lower high triglycerides. Also limit sugar, carbohydrate and alcohol intake. Alcohol has an especially strong effect on triglycerides. Repeated excessive drinking or even a single overindulgence can increase your triglycerides significantly. Binge drinking can cause a triglyceride spike that may trigger pancreatitis, a very painful and serious condition. But following your treatment regimen and these healthy guidelines can help prevent adverse health effects.