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Aims A genetic variant in LILRB5 (leukocyte immunoglobulin-like receptor subfamily-B) (rs12975366: T > C: Asp247Gly) has been reported to be associated with lower creatine phosphokinase (CK) and lactate dehydrogenase (LDH) levels. Both biomarkers are released from injured muscle tissue, making this variant a potential candidate for susceptibility to muscle-related symptoms. We examined the association of this variant with statin intolerance ascertained from electronic medical records in the GoDARTS study. Methods and results In the GoDARTS cohort, the LILRB5 Asp247 variant was associated with statin intolerance (SI) phenotypes; one defined as having raised CK and being non-adherent to therapy [odds ratio (OR) 1.81; 95% confidence interval (CI): 1.34–2.45] and the other as being intolerant to the lowest approved dose of a statin before being switched to two or more other statins (OR 1.36; 95% CI: 1.07–1.73). Those homozygous for Asp247 had increased odds of developing both definitions of intolerance. Importantly the second definition did not rely on CK elevations. These results were replicated in adjudicated cases of statin-induced myopathy in the PREDICTION-ADR consortium (OR1.48; 95% CI: 1.05–2.10) and for the development of myalgia in the JUPITER randomized clinical trial of rosuvastatin (OR1.35, 95% CI: 1.10–1.68). A meta-analysis across the studies showed a consistent association between Asp247Gly and outcomes associated with SI (OR1.34; 95% CI: 1.16–1.54). Conclusion: This study presents a novel immunogenetic factor associated with statin intolerance, an important risk factor for cardiovascular outcomes. The results suggest that true statin-induced myalgia and non-specific myalgia are distinct, with a potential role for the immune system in their development. We identify a genetic group that is more likely to be intolerant to their statins.

Aims: Plasma BNP and high-sensitivity cardiac troponin-T (hs-TnT) are elevated by both ischaemia and LV systolic dysfunction (LVSD). As a result, it is unknown whether BNP and/or hs-TnT could be useful biomarkers to identify ischaemia in the presence of LVSD., Methods and Results: Three separate patient populations were studied. Study A (n = 500) involved consecutive patients undergoing clinically indicated myocardial perfusion scintigraphy, study B (n = 100) included patients with vascular disease but no known cardiac disease, and study C (n = 300) recruited primary prevention patients with controlled risk factors. Levels of BNP and hs-TnT were measured prior to the stress testing to detect myocardial ischaemia. The prevalence of myocardial ischaemia was 28.2, 28, and 6.3% in study A, B, and C, respectively. For BNP, area under curve (AUC) values to identify ischaemia in the presence and absence of coincidental LVSD were: 0.73 vs. 0.63 (study A), 0.90 vs. 0.81 (study B), and 0.83 vs. 0.80 (study C). Equivalent figures for hs-TnT were: 0.64 vs. 0.60 (study A), 0.75 vs. 0.68 (study B), and 0.53 vs. 0.68 (study C). BNP and hs-cTnT, when combined together, performed better with an AUC of 0.75 vs. 0.65 (study A), 0.91 vs. 0.92 (study B), and 0.84 vs. 0.83 (study C)., Conclusion: In three separate populations a consistent finding is that BNP is increased further by myocardial ischaemia even in the presence of LVSD. A disproportionately high BNP for the degree of LVSD might be due to (unsuspected) ischaemia, and a disproportionately low BNP could be useful as a 'rule out' test for ischaemia even in the presence of LVSD., (First published online by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. © The Author 2013.)