The pronounced increase in global incidence of obesity has led to a high prevalence of its comorbidities, which are all major cardiovascular disease (CVD) risk factors. Patients with 3 or more obesity comorbidities (dyslipidaemia, hypertension, insulin-resistance/diabetes) have the metabolic syndrome (MetS) (Eckel et al., 2010), which greatly increases risk of developing coronary artery disease (Kannel et al., 1961), decreases myocardial tolerance to I/R (Bouhidel et al., 2008; Du Toit et al., 2008; Clark et al., 2011; Wensley et al., 2013) and increases the risk of cardiac death 2-4 fold (Lakka et al., 2002). In this growing population statin therapy is the cornerstone for management of dyslipidaemia and reduction of cardiovascular risk (Gu et al., 2014; O’Keeffe, Nazareth and Petersen, 2016). Although statins are highly effective for the maintenance of normal lipid levels, they also exert complex pleiotropic effects independent of lipid lowering actions (Zhou and Liao, 2009; Allen and Mamotte, 2017). As the single most prescribed cardiovascular drug (Stewart, 2017), it is important to delineate these pleiotropic actions and how chronic statins may modify disease processes in those that ultimately do suffer an ischaemic insult. We recently showed that myocardial tolerance to I/R in obesity is dependent on the presence or absence of insulin-resistance (Donner et al., 2013). Data suggest that isolated obesity and dyslipidaemia may actually protect the heart whereas obesity with insulin-resistance adversely impacts ischaemic tolerance in a rodent model of MetS (Donner et al., 2013). Cardioprotection with obesity has also been recently reported by others (Salie et al., 2014; Webster et al. 2017). Prolonged untreated dyslipidaemia and elevated circulating nonesterified fatty acids associated with obesity are implicated in the aetiology of insulinresistance and diabetes (Lopaschuk et al., 2007; Chess and Stanley, 2008). However, the efficacy of lipid lowering drugs for the prevention/attenuation of insulin-resistance is 3 controversial, with studies suggesting statins can decrease (Bellia et al., 2012; Sato et al., 2012), have no effect (Panz et al., 2012) or improve (Fraloub et al., 2012; Guo et al., 2012) insulin sensitivity in insulin-resistant/diabetic animals and patients.