AMSTERDAM – People with congenitally reduced triglyceride levels had about a 20% reduced risk of all-cause death compared with people without inherently low triglyceride levels during more than 30-years follow-up of nearly 14,000 people enrolled in the Copenhagen City Heart Study.
Data from the study also showed that people with higher triglyceride (TG) levels at the time they entered the study had significantly higher all-cause mortality during more than 30 years of follow-up than did people who entered with lower TG levels, Dr. Børge G. Nordestgaard said at the European Society of Cardiology annual congress.
But the result from the genetic analysis provided even more persuasive evidence that it is time to run a large, prospective intervention trial aimed at testing the preventive efficacy of TG lowering in patients selected based on elevated TGs, he said.
The genetic analysis "took advantage of nature’s randomized trial," said Dr. Nordestgaard, professor and chief of clinical biochemistry at Copenhagen University Hospital. The genetic analysis looked at long-term survival relative to the number of TG-lowering alleles each person had in their lipoprotein lipase genes. "These data suggest a causal relationship between low TGs and improved survival. Lots of drugs are available to lower triglycerides, such as atorvastatin and rosuvastatin, but so far all the trials only focused on high LDL or low HDL cholesterol. No trial enrolled patients on the basis of high triglycerides.
"A lot of people have normal LDL levels and high TGs, and right now they are ignored," he said. "Before statins, everyone talked about high LDL and high TGs as being equal risk factors, but now TGs are completely forgotten. A big mistake has been interpreting results from the statin trials, because the participants in those studies did not enter the trials because of their TG levels."
Dr. Nordestgaard and his associates performed an analysis of the hazard ratio for all-cause death among 13,957 people enrolled in the Copenhagen study. Compared with people who entered the study with a nonfasting serum triglyceride level of 266-442 mg/dL, 8% of everyone enrolled, those with a level of 177-265 mg/dL, 17% of enrollees, had an all-cause mortality rate that was relatively reduced by 10%, a statistically significant difference. People who entered with a TG level of 89-176 mg/dL, about half of the enrollees, had their relative mortality rate cut by 25% compared with the reference group, and those who entered with a level of less than 89 mg/dL, 22% of the enrollees, had a mortality rate that ran half that of the reference group, also statistically significant differences.
To better document an effect from reduced TG levels, the investigators used data that had been collected on six different genetic alleles in the gene coding for lipoprotein lipase linked to reduced TG levels. Data on allele numbers were available for 10,208 of the study participants, and those with 0-3 of the alleles were used as the reference group. People with four, five, or six of these alleles showed progressively larger drops in TG level; those with 4 of the alleles had a level about 10% below the reference group, those with five alleles were about 20% below, and those with six alleles had a TG level that averaged 30% below the reference group.
Mortality during follow-up tracked with TG levels at baseline and the number of TG-lowering alleles. People with 4 alleles had a mortality rate 15% below the rate among those with 0-3 alleles. People with five TG-lowering alleles had a 20% cut in mortality, and those with six alleles had a 22% reduction.
Dr. Nordestgaard said that he has been a consultant to 11 drug companies, including AstraZeneca, Merck, and Pfizer.
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