Which of the thousands of biomarkers associated with cardiovascular disease could actually become a useful drug target? Host Mitsuaki Sawano, MD, and co-host Nobuhiro Ikemura, MD, welcome Satoshi Yoshiji, MD, PhD (McGill University) to discuss a recent JACC study tackling this question in ischemic heart disease. Starting with 9,520 circulating proteins, the investigators used human genetics to move beyond association toward stronger evidence for causality, combining Mendelian randomization, genetic colocalization, multiple proteomic platforms, and cross-ancestry validation to narrow thousands of signals to a small group of potential therapeutic targets. We break down what these methods actually mean for clinicians: what cis-pQTLs tell us, why MR alone is not enough, what colocalization adds, and why validation across platforms and populations matters. The episode explores how this emerging approach could help determine which biological targets are worth pursuing in drug development and ultimately testing in clinical trials.

Hosts Mitsuaki Sawano, MD, Satoshi Shoji, MD, and Kentaro Ejiri, MD, welcome Yoshito Kadoya, MD, PhD (University of British Columbia / St. Paul's Hospital) to discuss his JACC: Cardiovascular Imaging study, "PET-Based Coronary Microvascular Dysfunction Phenotypes and Outcomes in Patients With Normal Myocardial Perfusion." Among 3,317 patients with normal relative perfusion on cardiac PET, the study examined four phenotypes defined by myocardial flow reserve and stress myocardial blood flow. Both classical CMD and endogen CMD were associated with higher long-term cardiovascular risk, suggesting that reduced MFR may remain clinically meaningful even when stress myocardial blood flow is preserved. The episode explores how PET can phenotype coronary microvascular dysfunction, differences between invasive and noninvasive approaches to CMD, and Dr. Kadoya's cardiac imaging training and career in Canada.

Host Mitsuaki Sawano, MD, welcomes Shuhei Nomura, PhD (Tohoku University), Lisa Yamasaki, MD (Harvard T.H. Chan School of Public Health), and Haruka Sakamoto, MD, PhD (St. Luke's International Hospital) to discuss two policy reviews published in The Lancet Regional Health – Western Pacific. Fifteen years after the 2011 Lancet Japan Series, Japan faces population aging, rising long-term care needs, workforce shortages, financial pressures, and a rapidly changing global health environment. The episode explores how Japan can shift from hospital-centered care toward prevention and community-based care while also rethinking its role in global health. The guests discuss why domestic reform and international collaboration must increasingly move together, and what Japan can learn from its neighbors as it prepares for 2040.