CD4+CD28null T lymphocyte frequency, a new marker of cardiovascular risk: Relationship with polycystic ovary syndrome phenotypes

Objective: To study the frequency of CD4⁺CD28^null T cells, which are aggressive T lymphocytes associated with recurrent coronary instability and type 2 diabetes mellitus, in different polycystic ovary syndrome (PCOS) phenotypes and in age- and body mass index-matched healthy women. Design: Retrospective cohort observational study. Setting: Unit of human reproductive pathophysiology, university hospital. Patient(s): A total of 167 PCOS patients and 102 control subjects. Intervention(s): None. Main Outcome Measure(s): CD4⁺CD28^null T cell frequency, high-sensitive C-reactive protein levels, and other glucose-metabolic parameters. Result(s): CD4⁺CD28^null frequency was significantly higher in all PCOS groups than in control subjects. CD4⁺CD28^null frequency was significantly higher in nonhyperandrogenic phenotype (5.7%, range 3.2-7.1) than in phenotypes with hyperandrogenism (H) + oligoamenorrhea (O) + polycystic ovary (PCO) (3.5%, range 1-5.8), H + O (3%, range 1.8-4.7), and H + PCO (2.63%, range 1.2-4.1). The relative risk of non-H phenotype for PCOS women in the highest quartile for CD4⁺CD28^null frequency compared with PCOS women with the lowest quartile was 3.2 (95% confidence interval 1.9-5.8). Conclusion(s): Cardiovascular risk evaluation should be performed in all PCOS phenotypes. In particular, we demonstrated that the non-H phenotype has potentially increased cardiovascular risk in terms of CD4 ⁺CD28^null frequency.