Patients with CHD who also have elevated triglycerides have an increased risk for all-cause mortality, independent of HDL, according to researchers.
Robert Klempfner, MD , of the Heart Center, Sheba Medical Center, Israel, and colleagues divided 15,355 patients from the Bezafibrate Infarction Prevention (BIP) trial into five groups of varying triglycerides levels: low-normal triglycerides (< 100 mg/dL), high-normal triglycerides (100 to 149 mg/dL), borderline hypertriglyceridemia (150 to 199 mg/dL), moderate hypertriglyceridemia (200 to 499 mg/dL) and severe hypertriglyceridemia ( 500 mg/dL).
The researchers matched the patients to death records in the National Population Registry to determine all-cause mortality during long-term follow-up.
The BIP trial
BIP was a multicenter, randomized, placebo-controlled, double blind trial that investigated whether long-term use of bezafibrate was effective in reducing coronary events. Enrollment occurred between February 1990 and October 1992. Eligible patients were aged 45 to 74 years with a history of MI within the past 5 years. Median follow-up was 22.8 years.
The study population for the long-term analysis included patients who participated in the trial and those who only went through the initial screening process (81% men; average age, 60 years). Seventy-two percent had a history of MI.
The researchers found elevated triglycerides more often in younger patients with higher BMI and diabetes. Those with high triglycerides also were more likely to be smokers and have NYHA class II or higher. Klempfner and colleagues noted that HDL was inversely associated with triglyceride levels (Spearman correlation coefficient = –0.41; P < .01) but apolipoprotein B was directly correlated with them (Spearman correlation coefficient for = 0.2; P < .01).
Mortality rose with triglycerides
After adjusting for age and sex, all-cause mortality rose as levels of triglycerides rose. Survival was 41% in the low-normal triglyceride group, 37% in the high-normal triglyceride group, 36% in the borderline hypertriglyceridemia group, 35% in the moderate hypertriglyceridemia group and 25% in the severe hypertriglyceridemia group (log-rank P < .001).
After adjustment for HDL, BMI and diabetes, the three highest groups had a 16% (borderline hypertriglyceridemia), 29% (moderate hypertriglyceridemia) and 68% (severe hypertriglyceridemia) increased mortality risk compared with patients in the lowest group. Even after adjusting for HDL, the association between triglycerides and increased long-term mortality remained.
The researchers wrote that although patients with severe hypertriglyceridemia had the most risk, even lowertriglyceride levels of 100 mg/dL to 149 mg/dL meant increased risk for all-cause mortality.
“The results published in our report support the renewed interest in triglycerides as a possible therapeutic target for [CV] risk reduction,” Klempfner and colleagues wrote.
“An interesting lesson could be derived from the BIP study; despite a significant HDL increase in the bezafibrate treatment arm, the overall benefits were nonsignificant. However, the benefit of bezafibrate in the subgroup of patients with high triglycerides levels was impressive,” they wrote.
Call for more research
The study findings may suggest the need for the addition of nonstatin therapy to standard of care lipid management to keep triglyceride levels in check, but “simply because something may or may not be a [CV] risk factor, altering it pharmacologically does not always mean that we will lower risk,” Karol E. Watson, MD, PhD, and Philipp Wiesner, MD, both of the division of cardiology at the David Geffen School of Medicine at University of California, Los Angeles, wrote in a related editorial.
Karol E. Watson
They cited trials such as ACCORD, AIM-HIGH and HPS-2 that not only suggested there was no benefit to additional lipid-altering drugs, but also that there could be risks to combining drugs as well. Current guidelines for cholesterol management do not recommend “adding triglyceride-lowering medication to statin therapy in patients with elevated triglycerides,” they wrote.
Although there have been recent trials investigating the safety and efficacy of a new “class of therapeutic agents, antisense inhibitors of apolipoprotein C-III” in reducing triglyceride levels, Watson and Wiesner wrote that it is too soon to know all the risks and benefits associated with this new pharmaceutical, and lifestyle intervention is still an effective strategy to improve CV outcomes. – by Tracey Romero
Disclosure: The researchers, Watson and Wiesner report no relevant financial disclosures.