Elevated Triglyceride Level Is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease

Abstract

Background-The independent association between elevated triglycerides and all-cause mortality among patients with established coronary heart disease is controversial. The aim of this study was to investigate this association in a large cohort of patients with proven coronary heart disease. Methods and Results-The study cohort comprised 15 355 patients who were screened for the Bezafibrate Infarction Prevention (BIP) trial. Twenty-two-year mortality data were obtained from the national registry. Patients were divided into 5 groups according to strata of fasting serum triglycerides: (1) low-normal triglycerides (<100 mg/dL); (2) highnormal triglycerides (100-149 mg/dL); (3) borderline hypertriglyceridemia triglycerides (150-199 mg/dL); (4) moderate hypertriglyceridemia triglycerides (200-499 mg/dL); (5) severe hypertriglyceridemia triglycerides (≥500 mg/dL). Ageand sex-adjusted survival was 41% in the low-normal triglycerides group than 37%, 36%, 35%, and 25% in groups with progressively higher triglycerides (P<0.001). In an adjusted Cox-regression for various covariates including high-density lipoprotein cholesterol, each 1 unit of natural logarithm (Ln) triglycerides 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 was increased by 68% when compared with patients with low-normal triglycerides (P<0.001). Conclusions-In patients with established coronary heart disease, higher triglycerides levels are independently associated with increased 22-year mortality. Even in patients with triglycerides of 100 to 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. (Circ Cardiovasc Qual Outcomes. 2016;9:100-108.

Rationale and design of REDUCE‐IT: Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial

“…Epidemiological, biological, and genetic studies have provided robust evidence of a strong association between elevated TG levels and higher rates of CV events 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. Furthermore, TG reduction lowers several inflammatory markers associated with CV risk, and subgroup and post hoc analyses of outcome studies suggest possible reductions in major CV events with TG‐lowering therapy 3, 4, 5, 6, 7, 8, 9, 10, 11.…”

“…1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24 Part of the reason may involve differences between the classes of drugs studied, such as fibrates, niacin, and omega‐3 fatty acids. Even among omega‐3 fatty acid studies, there are marked differences with respect to the relatively low doses of omega‐3 administered and the ratio of EPA to DHA 16, 17, 18, 19, 20, 21, 22, 23, 24.…”

“…Statin therapy has been well established as a cornerstone of cardiovascular prevention, and yet despite potent therapies for lowering low‐density lipoprotein cholesterol (LDL‐C), substantial residual risk remains 1, 2, 3. Clinical and epidemiological studies have demonstrated that triglyceride (TG) elevation is an independent risk factor for increased cardiovascular (CV) events, and therefore may represent one contributive factor of residual CV risk beyond statin therapy 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11.…”

“…Clinical and epidemiological studies have demonstrated that triglyceride (TG) elevation is an independent risk factor for increased cardiovascular (CV) events, and therefore may represent one contributive factor of residual CV risk beyond statin therapy 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11. More recently, elegant Mendelian randomization studies have supported a causal role for TG in the pathogenesis of cardiovascular disease (CVD), showing that elevated TG are not merely a risk marker, but rather a risk factor and thus potentially modifiable 3.…”

Slippery Slope of Triglycerides

“…In this issue of Circulation: Cardiovascular Quality and Outcomes, the article by Klempfner et al 4 adds further support for a role of triglycerides in promoting mortality, likely via an increase in CVD mortality. The article "Elevated Triglyceride Level is Independently Associated With Increased All-Cause Mortality in Patients With Established Coronary Heart Disease: A 22-Year Follow-Up of the BIP Study and Registry" reported long-term mortality data on 15 355 patients who were screened for the Bezafibrate Infarction Prevention (BIP) trial.…”