Elevated Triglyceride Level Associated With Increased All-Cause Mortality in Established CHD

Study Questions:

Is there an association between elevated triglycerides and long-term all-cause mortality among patients with established coronary heart disease (CHD)?

Methods:

The study cohort comprised 15,355 patients who were screened for the BIP (Bezafibrate Infarction Prevention) trial. Twenty-two–year mortality data were obtained from the national registry. Patients were divided into five groups according to strata of fasting serum triglycerides: 1) low-normal triglycerides (<100 mg/dl), 2) high-normal triglycerides (100-149 mg/dl), 3) borderline hypertriglyceridemia triglycerides (150-199 mg/dl), 4) moderate hypertriglyceridemia triglycerides (200-499 mg/dl), and 5) severe hypertriglyceridemia triglycerides (≥500 mg/dl). Patients with incident cancer were excluded.

Results:

Mean age was 60 years and 80% were male. Increased triglycerides were associated with lower age, smoking, hypertension, diabetes, CHD, increased heart rate and systolic blood pressure, lower high-density lipoprotein cholesterol (HDL-C), and higher glucose. Age- and sex-adjusted survival was 41% in the low-normal triglycerides group then 37%, 36%, 35%, and 25% in groups with progressively higher triglycerides, respectively (p < 0.001). In an adjusted Cox-regression for various covariates including HDL-C, each 1 unit of natural logarithm (Ln) triglyceride elevation was associated with a corresponding 6% (p = 0.016) increased risk of 22-year all-cause mortality. The 22-year mortality risk for patients with severe hypertriglyceridemia increased by 68% when compared with patients with low-normal triglycerides (p < 0.001). The fully multivariate adjusted model included adjustment for baseline glucose level >100 mg/dl.

Conclusions:

In patients with established CHD, higher triglyceride levels are independently associated with increased 22-year mortality. Even in patients with triglycerides of 100-149 mg/dl, the elevated risk for death could be detected than in patients with lower triglycerides levels, whereas severe hypertriglyceridemia denotes a population with particularly increased mortality risk.

Perspective:

The strength of the study is the 22-year duration of follow-up, but only a portion of patients in the BIP randomized clinical trial were included, and the results are based only on the single measure of laboratory variables. Also, treatments and the percentage developing diabetes, as well as the cause of death were not known. Nevertheless, the risk attributable to triglyceride levels occurred within the normal range and independent of HDL-C. The findings suggest a role for targeting triglycerides and very low-density lipoprotein metabolism with novel agents such as the apolipoprotein C-III inhibitors.

Clinical Topics: Diabetes and Cardiometabolic Disease, Clinical Topic Collection: Dyslipidemia, Prevention, Lipid Metabolism, Nonstatins, Hypertension, Smoking

Keywords: Bezafibrate, Blood Pressure, Cholesterol, HDL, Coronary Artery Disease, Diabetes Mellitus, Dyslipidemias, Glucose, Hypertension, Hypertriglyceridemia, Infarction, Lipoproteins, HDL, Mortality, Primary Prevention, Smoking, Triglycerides


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