In reply Ahmad and Garg have noted the similarity in the proportion of APOB R3500Q carriers and noncarriers with a history of self-reported cardiovascular events and questioned whether the lack of difference could be an artifact of survival bias or alternatively could reflect a lack of association between the mutation and excess cardiovascular morbidity, despite the mutation being associated with increased LDL-C levels and coronary artery calcification. We suspect that the mutation does have an impact on mortality rates based on our preliminary analysis of all-cause mortality in relatives of our study subjects whom we can infer to be mutation carriers. In our Amish population we identified 14 relatives of study subjects (mostly parents) who, although deceased, could unambiguously be inferred as APOB R3500Q carriers. The mean (SD) age at death in these 14 obligate carriers was 68.6 (15.6) years, with a range of 39 to 90 years. In contrast, we have estimated the mean (SD) age at death among Amish from Lancaster County, Pennsylvania, born between 1908 and 1920 to be 77.6 (13.5) years, based on 539 deaths. While we recognize that the number of deaths we have observed among obligate APOB R3500Q carriers is small, our best guess at present is that the APOB R3500Q mutation probably is associated with decreased lifespan and that the lack of difference in self-reported cardiovascular events observed between R3500Q carriers and noncarriers in our study is probably an artifact of the relatively young age of many of our study subjects and/or a survival bias. The question as to whether the R3500Q mutation might have differential effects on men vs women is an interesting one. We found no statistical evidence that the strength of the association between the R3500Q mutation and either LDL-C levels or coronary artery calcification presence differed between men and women, although it is possible that the variant may have more severe effects on mortality or CVD incidence in men than in women. Correspondence: Dr Mitchell, Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, 660 W Redwood St, Room 492, Baltimore, MD 21201 (firstname.lastname@example.org). Financial Disclosure: None reported.
Archives of Internal Medicine – American Medical Association
Published: Jun 13, 2011
Keywords: cardiovascular diseases,apolipoproteins b
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