Author + information
- Cian P. McCarthy, MBBCh, BAO and
- John W. McEvoy, MBBCh, MHS∗ ()
- ↵∗Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, and Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Blalock 524C, 600 North Wolfe Street, Baltimore, Maryland 21287
In their analysis of the WOSCOPS (West of Scotland Coronary Prevention Study), Ford et al. (1) evaluated the utility of serial high-sensitivity troponin (hsTn) measurement in assessing response to 40 mg of pravastatin and in predicting risk for future coronary events among hypercholesterolemic men. They found that hsTn was reduced by statin and that the magnitude of this reduction correlated with risk of coronary events (1). Surprisingly, the authors also reported that reduction in low-density lipoprotein (LDL) cholesterol with statin was not an indicator of relative benefit in their cohort. These findings are provocative in that they position hsTn as a dynamic marker of response to statin therapy and suggest the benefit of statins may not be mediated by LDL cholesterol.
However, we worry the investigators may misrepresent the benefit of LDL cholesterol reduction. Although they found no significant association between decrease in LDL cholesterol and relative reduction in coronary events, there is irrefutable evidence from multiple meta-analyses that absolute LDL cholesterol concentration is linearly associated with absolute risk for coronary events and that the larger the reduction in LDL cholesterol concentration achieved with statin, the lower the absolute event rate (2,3). Prior data from WOSCOPS have demonstrated this phenomenon (Figure 1).
This apparent contradiction may reflect differences in analytic approach. The models presented in the study’s Table 2 (1) adjust for both baseline hsTn and change in hsTn, a strategy that may mask the benefit of LDL reduction if the salutary effects of cholesterol treatment are mediated by reductions in coronary ischemia. That relative reduction in LDL cholesterol was associated with clinical benefit in models that were not adjusted for hsTn (Online Table 3 ) appears to support this (e.g., hazard ratios for events ranging from 0.39 to 0.53, depending on magnitude of LDL cholesterol reduction [all p values <0.05]).
When reporting results that contradict prior data, it is important to consider the effects of the exposure on absolute event rates and not just on statistically adjusted relative measurements of effect size.
Please note: Both authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2017 American College of Cardiology Foundation
- Ford I.,
- Shah A.S.V.,
- Zhang R.,
- et al.
- Silverman M.G.,
- Ference B.A.,
- Im K.,
- et al.
- O'Keefe J.H. Jr..,
- Cordain L.,
- Harris W.H.,
- Moe R.M.,
- Vogel R.