Telomere Length: An Independent Risk Factor for Premature MI?
To the Editor:
We read with great interest the recent report by Brouilette et al1 on white cell telomere length and risk of premature myocardial infarction. We agree with the authors that the findings have the potential to be of great importance in understanding the etiology of coronary heart disease and in distinguishing biological from chronological aging. We were, however, concerned about two points in the analysis.
First, in Table 2, the effect of CHD risk factors on telomere length is displayed with adjustment for case status. Each of these variables differs between cases and controls, as does telomere length. The analysis controls for case status, and the results are presented as evidence for lack of a significant relationship between each of these factors and telomere length. We are concerned that, because the CHD risk factors are so different between cases and controls, adjusting for case status may artificially attenuate the effect of the risk factor on telomere length. We would like the authors to present a stratified analysis so that the effect of CHD risk factors on telomere length can be assessed in cases and controls separately.
Second, Figure 2 and the corresponding analysis are presented without apparent adjustment for age, sex, and the other CHD risk factors. While we are confident that the relationship will remain the same, we feel that it is necessary to present the adjusted analysis to fully support the authors’ claim of the independence of effects of telomere length and age.
We look forward to the authors’ reply and to more research on the concept of biological aging.
- ↵Brouilette S, Singh RK, Thompson JR, Goodall AH, Samani NJ. White cell telomere length and risk of premature myocardial infarction. Arterioscler Thromb Vasc Biol. 2003; 23: 842–846.
We thank Paynter and Watkins for their interest in our article. They request an expanded version of our original Table 2, which we are happy to provide (see Table). The expanded version contains the original analysis adjusted for case-control status and the separate analyses for cases and for controls (excluding those related to cholesterol and family history, which were carried out in only one group). It will be evident that the adjusted figures quoted in our article are in effect weighted averages of the results for cases and for controls. The final column is a test of difference between cases and controls in their effect on TRF length.
The full analysis of this study produced a vast number of probability values, so we must guard against over-interpreting every one that gets close to 0.05. The only difference between cases and controls that is perhaps notable is that associated with current smokers compared with nonsmokers (interaction P=0.03). In cases, current smokers have shorter TRF lengths (P=0.06), whereas in controls, current smokers have longer TRF lengths (P=0.15). There is no corresponding pattern in ex-smokers or when smoking is analyzed by number of pack years. While one can always invent reasons behind an observed difference in a data set, we had no prior reason to expect this particular pattern and feel that it is probably just a chance effect. Although further works needs to be done on the effect of acquired cardiovascular risk factors on telomere length, we would like to emphasize that in our study the relationship between telomere length and risk of premature myocardial infarction (MI) was independent of the measured risk factors.
Regarding Figure 2, after adjustment for age, sex, and the other risk factors, the odds ratios of MI are as follows: compared with subjects in the highest quartile for TRF, the odds ratios were 1.98 (95% CI, 0.92 to 4.29, P=0.082), 3.09 (95%CI, 1.40 to 6.80, P=0.003), and 3.34 (95%CI, 1.50 to 7.43, P=0.002), respectively in subjects in the second, third, and lowest quartile of mean TRF length. As anticipated by Paynter and Watkins, the adjustment makes little difference to the association.
We hope this additional information is helpful. We agree with Paynter and Watkins that the concept of biological ageing has considerable potential for understanding the etiology of coronary heart disease.