CD4(+)CD28(null) 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.