In Reply We appreciate the interest in our recent article demonstrating the association of high levels of physical activity (>3000 metabolic equivalent of task–minutes/week), coronary artery calcification (CAC), and mortality in 21 758 men with a normal maximal treadmill exercise test and no history of clinical coronary heart disease (CHD).1 Shaikh and Budoff emphasized that higher levels of CAC (100 Agatston units [AU] or greater) were associated with higher event rates compared with those with CAC less than 100 AU regardless of physical activity volume. We agree with this observation, which we consider settled science, based on data from the Budhoff et al team2 as well as our own.3 However, the primary intent of the current analysis was to examine the mortality risk of clinically meaningful levels of elevated CAC in patients who have very high volumes of physical activity. Prior studies have found that high volumes of physical activity are associated with greater levels of CAC, but these studies had neither the number of participants nor sufficient follow-up to evaluate mortality risk.4,5 In the current study, the key take-home message was that among those with clinically significant levels of CAC, higher volumes of physical activity were not associated with a greater risk of dying. Indeed, the point estimate for relative risk raised the possibility of a reduced risk of death compared with those with equivalent amounts of CAC but low levels of physical activity. However, because of relatively lower numbers (only approximately 25% of each physical activity group had CAC greater than 100 AU), this reduction was not as robust and compelling as the comparison among those with CAC less than 100 AU. We also emphasize that as noted in Table 2,1 the absolute amount of CAC in those in our high CAC group was quite high and not different among physical activity groups, despite the slightly higher risk (11%) of the high-volume exercisers having a CAC greater than 100 AU. We refer Shaikh and Budoff (and all readers) to our online Supplement (eTables 5 and 6 in the Supplement1), where we provide additional data showing that other cut points, such as CAC greater than 0 AU and of 400 AU and greater, do not change this fundamental message.
DeFina LF, Radford NB, Levine BD. Risks of High Coronary Artery Calcium—Reply. JAMA Cardiol. Published online May 15, 20194(7):713. doi:10.1001/jamacardio.2019.1406
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