Editorial: HDL and cardiovascular disease: mechanisms, clinical relevance, and therapeutic impacts

that variations in HDL function likely have great impact on vascular and metabolic health, and more recent research efforts have been placed on enhancing our understanding of HDL mechanisms of Thisaction. This Research Topic explores a broader understanding of HDL, highlighting its role in CVD, its biological complexity, and its potential impact on treatment strategies.Combining HDL with other lipid markers can improve cardiovascular risk prediction. Jiawei Zhang et al. conducted a cross-sectional clinical study demonstrating that the non-HDL-C/HDL-C ratio is associated with higher abdominal aortic calcification (AAC) scores and a greater risk of severe AAC 11 . In a prospective cohort study, Luqing Liu et al. included 43,735 participants and further showed that an elevated cumulative non-HDL-C-to-HDL-C ratio is significantly associated with an increased risk of cardiometabolic disease, independent of single-time-point measurements 12 . Similarly, Honglian Luo et al. reported in a prospective cohort study that both the log-transformed platelet-to-HDL-C ratio and its cumulative exposure are independently associated with higher cardiovascular disease risk, and that they provide modest incremental predictive value beyond baseline models 13 . Collectively, these findings support the concept that lipid-related composite indices may outperform HDL-C alone in capturing cardiovascular risk.Metabolic context beyond traditional phenotypes. Although not directly focused on HDL metabolism, Jiejie Xie et al. analyzed 4,440 adults with normal body mass index (BMI) and demonstrated significant associations between triglyceride-glucose-related indices and adverse clinical outcomes in individuals with normal BMI 14 . These findings suggest that insulin resistance may be present even in non-obese populations and highlight the need to interpret HDL-related risk within a broader metabolic context.sequencing in patients with very low HDL-C, identifying rare genetic variants that may contribute to low HDL-C syndrome 15 . These results underscore the heterogeneity of HDL and emphasize its underlying genetic and biological complexity. Therapeutic implications. Zhantao Cao et al. performed a systematic review and meta-analysis demonstrating that the combination of PCSK9 inhibitors and statin therapy significantly reduces major adverse cardiovascular events and improves lipid profiles in patients following percutaneous coronary intervention compared with statin monotherapy 16 . These findings suggest that cardiovascular benefit is achieved through comprehensive lipid modulation rather than targeting HDL alone.In summary, this Research Topic helps us better understand HDL by showing that it is more than just a simple biomarker and deserves renewed attention. By combining insights from genetics, new biomarker approaches, population studies, and clinical treatments, these studies offer a clearer direction for future research and support better ways to assess cardiovascular risk and guide patient care.