We appreciate the interest in our work (1) and thoughtful letter by Dr. Grant (2). The first point raised in his letter is the concern that adjusting for baseline levels of parathyroid hormone may not accurately capture mediation at the time of the event. We would like to point out that the difference in age between cases and controls did not change over time. Thus, any effect of age on parathyroid hormone levels would have been the same at baseline as it was at the time of the event.
The second point raised in the letter (2) is whether the analysis should be repeated with cutpoints for serum 25-hydroxyvitamin D (25(OH)D) levels of less than 15, 15–30, and greater than 30 ng/mL. We chose the cutpoint of 20 ng/mL because it is both a clinically relevant cutpoint and also corresponds with an empirical cutpoint (based on the spline, Figure 1) (1). As stated in paragraph 2 of our results section, “The question of whether 25(OH)D levels of 20–29.9 ng/mL (often referred to as vitamin D insufficiency) also confer adverse health consequences is currently controversial. Therefore, we performed additional exploratory analyses to compare annual cardiovascular event rates at 3 different 25-OH levels: <20 ng/mL, 20–29.9 ng/mL, and ≥30 ng/mL. These analyses confirmed that the cardiovascular event rates observed in participants with 25(OH)D levels of 20–29.9 ng/mL were similar to the rates observed in participants with 25(OH)D levels greater than or equal to 30 ng/mL (Figure 2)” (1, p.1281).
Acknowledgments
Conflict of interest: none declared.
Contributor Information
Christine C. Welles, Department of Medicine, University of California, San Francisco, CA Section of General Medicine, Veterans Affairs Medical Center, San Francisco, CA.
Mary A. Whooley, Department of Medicine, University of California, San Francisco, CA Section of General Medicine, Veterans Affairs Medical Center, San Francisco, CA; Department of Epidemiology and Biostatistics, University of California, San Francisco, CA.
S. Ananth Karumanchi, Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
Tammy Hod, Division of Nephrology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA.
Ravi Thadhani, Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA.
Anders H. Berg, Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA
Joachim H. Ix, Veterans Affairs San Diego Healthcare System, San Diego, CA Division of Nephrology, Department of Medicine, University of California, San Diego, CA; Department of Family and Preventive Medicine, University of California, San Diego, CA.
Kenneth J. Mukamal, Division of General Medicine and Primary Care, Beth Israel Deconess Medical Center, Boston, MA
References
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