High triglycerides predict increased mortality in coronary heart disease

By Will Boggs MD

NEW YORK (Reuters Health) - Elevated triglyceride levels are independently associated with increased all-cause mortality in patients with coronary heart disease (CHD), according to results from the Bezafibrate Infarction Prevention (BIP) Study and Registry.

There is a long-running controversy about the independent association between elevated triglycerides, cardiovascular risk, and mortality, with most studies showing a significant association between elevated triglycerides and adverse outcomes.

Dr. Aharon Erez, from Sheba Medical Center, Tel-Hashomer, Israel, and colleagues used data from 15,355 patients with proven CHD included in the BIP study and registry to clarify the association between different triglyceride levels and long-term (>22 years) all-cause mortality.

Age- and sex-adjusted survival showed a significant decreasing trend from 41% in the low-normal triglycerides group (100 mg/dL) to 37% with 100-149 mg/dL, 36% with 150-199 mg/dL, 35% with 200-499 mg/dL, and 25% with severe hypertriglyceridemia (500 mg/dL)(log-rank P<0.001), according to the March 8 Circulation: Cardiovascular Quality and Outcomes online report.

When assessed as a continuous variable, each unit increment in the natural logarithm (Ln) triglycerides was independently associated with 26% greater mortality, and this association remained significant after including high-density lipoprotein (HDL) cholesterol in the model.

In a Cox-regression fully adjusted model, each unit of Ln triglycerides elevation was associated with a 6% increased risk of all-cause mortality.

Elevated triglycerides were associated with mortality in all analyzed subsets (diabetes, low HDL cholesterol, high body mass index, and smoking) with the exception of the relatively small group of female patients (19% of the study population).

"The current threshold for the definition of elevated triglycerides level for patients with CHD may be higher than desired," the researchers concluded. "Prospective studies in appropriately selected subjects should further clarify these important aspects."

"Although we search for the true significance of elevated triglycerides in cardiovascular risk and potentially the optimal method to lower triglycerides, we congratulate (the authors) on an important study, which provides support for the idea that triglycerides should be considered more seriously as a future target to improve our patients' outcomes," wrote Dr. Karol E. Watson and Dr. Philipp Wiesner from David Geffen School of Medicine at UCLA, Los Angeles, in a related editorial.

"Be reminded, however, that we currently do not know if triglyceride elevations will hold similar predictive value in patients whose LDL (low-density lipoprotein) cholesterol is optimally controlled. And we must always remember that simply because something may or may not be a cardiovascular risk factor, altering it pharmacologically does not always mean that we will lower risk," they wrote.

Dr. Borge Nordestgaard, from the University of Copenhagen, Herlev, Denmark, who recently reviewed the association between triglycerides and cardiovascular disease (http://bit.ly/1RyKId8), told Reuters Health by email, "I find it surprising that the results are so clear-cut, that is, the higher the triglycerides at baseline the higher the all-cause mortality over 22 years -- despite that many of these patients surely were being treated with various lipid-lowering drugs over the past 22 years. The marked 68% increased all-cause mortality in patients with triglycerides over 500 mg/dL is also a striking finding."

"The explanation for the findings likely is due to the cholesterol content of triglyceride-rich lipoproteins, also called remnant cholesterol," Dr. Nordestgaard explained. "Incidentally, in a paper that just came online in Clinical Chemistry, we showed that elevated remnant cholesterol, just like elevated triglycerides but in contrast to elevated LDL cholesterol, is associated strongly with increased risk of all-cause mortality in patients with established coronary heart disease (like the patients in this study)."

"If you only are concerned with lowering of LDL cholesterol in high-risk patients, then your patients with high triglycerides may still have high risk of all-cause mortality," he concluded. "Physicians should consider drugs to not only lower LDL cholesterol but also triglycerides in high risk patients with elevated levels."

Dr. Erez did not respond to a request for comments.

The authors reported no funding or disclosures.

SOURCE: http://bit.ly/1M5mdT4 and http://bit.ly/1LbYDct

Circ Cardiovasc Qual Outcomes 2016.

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