Novel therapies targeting CETP along with other approaches to increase HDL‐C are currently under active investigation in an effort to reduce the risk of CAD.33 Because the cerebral small vessel diseases that lead to ICH are common in the aging population and frequently coincide with risk factors for cardiometabolic disease,34, 35 our observations supporting opposing effects of HDL‐C on ICH and CAD underscore the need for a better understanding of which patients could be at increased risk of ICH on therapies aimed at increasing HDL‐C. Here, CETP is linked to cerebral small vessel disease.