A higher serum lactate dehydrogenase to creatine phosphokinase ratio after exertional heat illness is associated with short-term heat intolerance

Heat intolerance (HI) after exertional heat illness (EHI) is assessed by heat tolerance testing (HTT), but predictive biomarkers are lacking. We evaluated whether the serum lactate dehydrogenase to creatine phosphokinase (LDH/CPK) ratio, measured early after collapse, is associated with short-term HI. We conducted a case-control study of 78 Israel Defense Forces soldiers with EHI who underwent HTT within six months and had LDH and CPK measured within 12 hours of collapse. Multivariable logistic regression estimated adjusted odds ratios, with Firth penalized regression as a parallel robustness analysis. Discrimination was assessed by receiver operating characteristic analysis. Nineteen (24.4%) were heat intolerant. The HI group had a higher ratio (median 1.14 vs. 0.69, p = 0.003). After adjustment, a higher ratio was associated with HI (OR 2.66, 95% CI 1.42 to 5.91); the penalized estimate was 2.23 (1.28 to 4.52). The area under the curve was 0.73 (0.59 to 0.85), better than either enzyme alone, but no cut-point was usable in isolation (sensitivity 63%, specificity 75% at 0.97). The ratio did not differ between heat stroke and heat exhaustion (p = 0.44), and remained associated with HI in those with altered mental status (OR 2.63, 1.31 to 7.35). A higher LDH/CPK ratio shortly after EHI is associated with short-term HI. The tissue source of the LDH elevation was not determined; central nervous system involvement remains one possible explanation, though it cannot be verified. The ratio is a candidate adjunct to return-to-duty assessment, and requires external validation.