Triglyceride Levels in Sons of Patients with Coronary Artery Disease

TO THE EDITOR:

We thank Dr. Grundy [1] for his supportive and useful discussion of our report [2], in which he considers various explanations for the prolonged postprandial hypertriglyceridemic response in the sons of patients with coronary artery disease. Dr. Grundy suggests that we examine the possible bimodality of responses in the offspring of patients, a bimodality that would theoretically emerge if group differences could be attributed to a heterozygous monogenic defect of triglyceride metabolism in patients. Given this monogenic hypothesis, a subgroup of patients having the gene would transmit it to 50% of their offspring. Consequently, a subgroup of sons would have marked postprandial responses, and Dr. Grundy suggests that these responses may explain the effect that we found.

A classic debate between Platt and Pickering (reviewed in reference 3) on the mode of transmission of primary hypertension on the basis of the shapes of blood pressure distribution curves has shown that bimodality, as distinct from left-skewing, in such curves is not easily proved. Further, a familially acquired abnormality in only a subgroup of families could theoretically lead to a similar bimodality. This and the relatively small sample size of our study initially led us not to engage in such an analysis. An alternative approach in unravelling putative modes of inheritance is segregation analysis, but such an analysis would not be overly informative in this case because of the limited number of siblings in our study. Nevertheless, we have attempted to address Dr. Grundy's suggestion. Figure 1 shows the frequency distribution of areas under the curve of the triglyceride response for sons of patients 6 to 12 hours after lipid loading. Although not a normal distribution, the number of observations does not allow definite conclusions on modality. Moreover, if those with a response above the arrow (n = 7) are excluded from the analysis, the difference between offspring groups remains of borderline significance (difference, 0.78 mmol x h/L; 95% CI, −0.015 to 1.574). Thus, it seems that offspring group differences cannot be fully explained by a subgroup of sons of patients with markedly high postprandial responses. Although this analysis must be evaluated with some caution, the monogenic mechanism as the sole explanation for prolonged postprandial hypertriglyceridemia does not appear to be supported by our data.

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Figure 1. t6-t12 = triglyceride responses 6 to 12 hours after lipid loading. Patients with responses higher than that indicated by the arrow were excluded from the analysis. Frequency distribution of area under the curve (1 mmol x h/L intervals) for sons of patients with coronary artery disease.

• Copyright ©2004 by the American College of Physicians