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Etiology

High triglyceride levels were associated with increased CHD in white men

ACP J Club. 1998 Sep-Oct;129:50. doi:10.7326/ACPJC-1998-129-2-050


Source Citation

Jeppesen J, Hein HO, Suadicani P, Gyntelberg F. Triglyceride concentration and ischemic heart disease. An eight-year follow-up in the Copenhagen Male Study. Circulation. 1998 Mar 24;97:1029-36.


Abstract

Question

Are triglyceride levels associated with an increased risk for coronary heart disease (CHD) in white men?

Design

8-year cohort study of white men in the Copenhagen Male Study.

Setting

A workplace study in Denmark.

Participants

3387 white men (mean age 63 y) were enrolled between 1985 and 1986. Exclusion criteria were a history of myocardial infarction, angina pectoris, stroke, or intermittent claudication.

Assessment of risk factors

Fasting triglyceride levels were measured at baseline, and participants were divided evenly into 3 groups: low, medium, and high (Table). The lowest level was given the relative risk (RR) of 1.0. Total, high-, and low-density lipoprotein (HDL and LDL) cholesterol levels were also measured. Other risk factors evaluated were alcohol and tobacco use, physical exercise, body mass index, systolic and diastolic blood pressure, hypertension, type 2 diabetes mellitus, glucosuria, and socioeconomic status. These were used in multivariate analyses to determine the independent association between triglyceride levels and CHD.

Main outcome measures

National databases were used to collect data on incidence of disease, hospital admissions, and deaths.

Main results

In the tertile analysis but not the logistic regression analysis, patients with the 2 highest triglyceride levels had an increase in the risk for CHD after adjustment for other nonlipid risk factors and HDL and LDL cholesterol levels (Table). When HDL cholesterol levels were categorized into 3 groups, the risk for CHD increased in an additive manner; the greatest risk was in men with the highest level of both triglycerides and HDL cholesterol (RR 2.7, 95% CI 1.2 to 6.0). All-cause mortality was not associated with levels of triglycerides (P = 0.06 for trend).

Conclusion

High levels of triglycerides were associated with an increased risk for coronary heart disease but not for all-cause mortality in middle-aged, white men.

Sources of funding: King Christian X Foundation; Danish Medical Research Council; Danish Heart Foundation; Else & Mogens Wedell-Wedellsborg Foundation.

For correspondence: Dr. J. Jeppesen, Copenhagen Male Study, Epidemiological Research Unit, Copenhagen University Hospital, Bispebjerg, Bispebjerg Bakke 23, DK-2400 Copenhagen NV, Denmark. FAX 45-35-327070.


Table. Incidence and univariate relative risk for mortality from coronary heart disease by tertiles of triglyceride levels in middle-aged, white men

Triglyceride levels Incidence Relative risk (95% CI) P value
Low (0.44 to 1.09 mmol/L) 4.6% 1.00 (reference standard)
Medium (1.10 to 1.59 mmol/L) 7.7% 1.5 (1.0 to 2.3) < 0.05
High (1.60 to 22.4 mmol/L) 11.5% 2.2 (1.4 to 6.0) < 0.001

Commentary

Measurement of a risk factor, such as triglyceride level, serves 2 possible functions. First, if the risk factor plays a causal role in CHD, it could become a target of treatment. Second, regardless of causality, measurement of the risk factor may help to predict absolute risk in an individual patient and hence target patients for treatment who are at higher risk. This study, like several others, shows that triglyceride levels are predictive of CHD but that CHD does not contribute to discernment of risk once other commonly accepted risk factors have been included: The univariate RR, per 1.0 mmol/L increase, of 1.4 (CI 0.8 to 2.1) changes to 1.0 (CI 0.2 to 1.8) in the multivariate analysis (1). Thus, triglyceride levels are not currently useful clinically as part of a combined risk prediction model. However, as Jeppesen and colleagues point out, this may reflect statistical problems caused by the skewed distribution of triglyceride levels and their variability, or it could be because only some components of triglyceride metabolism are involved in CHD. Thus, a causal role is still possible.

Is there evidence for a treatment effect? Fibrates can substantially lower triglyceride levels . The Helsinki Heart Study suggested that only the subgroup with high triglyceride and low HDL cholesterol levels showed a substantial risk for CHD and received the most benefit from gemfibrozil treatment (2). Further, it was suggested that triglyceride levels interact with other risk factors for CHD. A small, randomized trial of bezafibrate showed reduction in coronary events and angiographic progression. This study showed only a 9% reduction in serum cholesterol levels; however, both triglyceride and very low density lipoprotein cholesterol levels were reduced by 31% (3).

Where does this leave the clinician in practice? Despite these tantalizing findings, triglyceride measurement will still play only a minor role in risk prediction, and the causal role is insufficiently substantiated for triglyceride levels to become a therapeutic target. However, clinicians must keep an open mind that triglyceride levels may eventually be identified as important for the prevention of CHD.

Paul Glasziou, MBBS, PhD
University of Queensland, BrisbaneHerston, Queensland, Australia

Paul Glasziou, MBBS, PhD
University of Queensland, Brisbane
Herston, Queensland, Australia


References

1. NIH Consensus conference. Triglyceride, high-density lipoprotein, and coronary heart disease. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and Coronary Heart Disease. JAMA. 1993;269:505-10.

2. Tenkanen L, Pietila K, Manninen V, Manttari M. The triglyceride issue revisited. Findings from the Helsinki Heart Study. Arch Intern Med.1994;154:2714-20.

3. Ericsson CG, Hamsten A, Nilsson J, et al. Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients. Lancet. 1996;347:849-53.