1588 Arterioscler Thromb Vasc Biol September 2017 study of 2571 black participants from the SPRINT (Systolic Blood Pressure Intervention Trial) failed to demonstrate an association between high-risk APOL1 genotypes and CVD, despite showing a strong association with CKD. 20 Similarly, investigators with the ARIC study (Atherosclerosis Risk in Communities) found a strong association between the highrisk APOL1 genotype and end-stage renal disease but failed to demonstrate any association with incident CVD in 3676 black participants. 21

The discovery of the association of APOL1 variants with CKD was an exciting start to a story that is still unfolding. The question remains as to whether there is a link between APOL1 risk genotypes and CVD and if so, if it is distinct from a pathway to CVD driven by impairment in renal function (Figure). The results reported by Chen et al17 alone do not offer a definitive answer but rather provide one more piece to the puzzle. Given the wealth of data available, a meta-analysis of the existing literature offers a path forward to clarifying the true association between APOL1 and CVD. One of the challenges of assessing the present collection of studies, and in contemplating a meta-analysis, however, is the heterogeneity of outcomes used to define CVD and the range of underlying pathophysiological processes these represent; almost every published study has used a different composite CVD definition. Accordingly, future studies that evaluate APOL1 risk genotypes will need to carefully define outcomes. Electronic health records–based cohorts that allow for detailed phenotyping at a population scale represent a second pathway to elucidating the relationship between APOL1 and CVD. Such cohorts will have the sample sizes large enough to provide the necessary statistical power to