Cardio-Oncology in Cold Climates: Epidemiological Features, Bidirectional Interaction Mechanisms, and Integrated...

Cardiovascular disease (CVD) and cancer are leading causes of death worldwide, with their comorbidity posing a major public health challenge. In cold regions (latitude ≥ 45° or annual mean temperature ≤ 10 °C), this dual burden is exacerbated by unique environmental exposures and lifestyle factors. This review aims to systematically characterize the epidemiological features of CVD and cancer in cold regions, elucidate the mechanisms by which cold exposure synergistically exacerbates cancer therapy-related cardiovascular toxicity (CTR-CVT), and propose a comprehensive, cold-region-tailored management framework for the prevention, treatment, and rehabilitation of cardio-oncology comorbidity. Cold regions show significantly higher age-standardized incidence and mortality rates for both CVD and cancer compared to temperate regions. Low temperatures, high-sodium diets, and air pollution synergistically increase cardiovascular risk, while lung, colorectal, breast, and prostate cancers substantially exceed global averages. The bidirectional interaction between CVD and cancer involves multiple mechanisms. Cancer therapies induce cardiotoxicity via oxidative stress, mitochondrial dysfunction, ferroptosis, and inflammatory pathways. Conversely, CVD promotes cancer progression through chronic inflammation, neurohormonal activation, cardiac-derived factors, and exosome-mediated communication. Cold stress, acting as a synergistic toxicological factor, exacerbates comorbidity through sympathetic overactivation, amplification of oxidative and inflammatory cascades, and metabolic remodeling that disrupts drug metabolism and myocardial energy supply. In conclusion, CVD-cancer comorbidity in cold regions represents a distinct entity shaped by environmental and lifestyle factors. We propose a full-cycle, cold-region-tailored management system including cold adaptation training, dietary modification, vitamin D supplementation, integrated traditional Chinese and Western medicine, and dynamic monitoring of cardiometabolic and tumor markers. Future research should prioritize large-scale prospective studies, multi-omics approaches for sensitive biomarker identification, and region-specific interventions to reduce this dual disease burden.