Elevated triglycerides increase risk of long-term mortality

After a follow-up period of more than 22 years, patients with coronary heart disease who have an elevated triglycerides level have an increased risk in long-term mortality even after adjusting for cholesterol levels and other factors, according to an analysis of a secondary prevention prospective multicenter randomized, placebo-controlled, double-blinded trial.

Lead researcher Robert Klempfner, MD, of The Heart Center at Sheba Medical Center in Israel, and colleagues published their results online in Circulation: Cardiovascular Quality and Outcomes on March 8.

In this analysis, the researchers analyzed participants from the BIP (Benzafibrate Infarction Prevention) study, which screened and enrolled patients between Feb. 1, 1990, and Oct. 30, 1992. Patients were between 45 and 74 years old, had a history of MI from six months to five years before inclusion and had stable angina pectoris or related coronary artery disease, myocardial ischemia or at least 60 percent stenosis of one major coronary artery. They were excluded if they had diabetes that required insulin use, severe heart failure, unstable angina, hepatic or renal failure and current use of lipid-modifying medications.

The 15,355 patients were followed for a median of 22.8 years. The mean age was 60 years old, while 81 percent of patients were men and 72 percent had a previous MI.

The researchers placed the patients in five groups based on fasting serum triglycerides at screening: low-normal triglycerides (less than 100 mg/dL); high-normal trigylcerides (100 to 149 mg/dL); borderline hypertriglyceridemia triglycerides (150 to 199 mg/dL); moderate hypertriglyceridemia (200 to 499 mg/dL); and severe hypertriglyceridemia triglycerides (at least 500 mg/dL). They also defined low high-density lipoprotein (HDL) cholesterol as less than 40 mg/dL for men and less than 50 mg/dL for women.

Patients in the higher triglycerides groups were younger, had a higher body mass index (BMI) and a greater prevalence of diabetes and active smoking. The researchers added that peripheral vascular disease, chronic obstructive lung disease, past cerebrovascular accident or transient ischemic attack and other comorbidities were not significantly different among the groups.

After adjusting for age and sex, the survival rates were 41 percent in the low-normal triglycerides group, 37 percent in the high-normal trigylcerides group, 36 percent in the borderline hypertriglyceridemia triglycerides group, 35 percent in the moderate hypertriglyceridemia group and 25 percent in the severe hypertriglyceridemia triglycerides group.

Compared with a reference group with triglyceride levels below 100 mg/dL, those in the borderline hypertriglyceridemia triglycerides group had a 16 percent increased mortality risk, those in the moderate hypertriglyceridemia group had a 29 percent increased mortality risk and those in the severe hypertriglyceridemia triglycerides group had a 68 percent increased mortality risk. These results were based on multivariate Cox-proportional hazards regression modeling after adjusting for age, HDL cholesterol, BMI and the presence of diabetes.

The researchers cited a few limitations of the study, including that they had limited follow-up data and could not adjust for morbidity, treatment given and other potential confounders during the entire follow-up period. They also did not have information on the cause of death. Further, they based patients’ diabetes status on medical records obtained at baseline and only measured fasting triglyceride levels once, so they could not adjust for possible variations over time. In addition, the study had a lack of racial/ethnic diversity, which was limit the generalizability of the findings.

“The current threshold for the definition of elevated triglycerides level for patients with [coronary heart disease] may be higher than desired,” the researchers wrote. “Prospective studies in appropriately selected subjects should further clarify these important aspects.”