Sukupuolen vaikutus merkitykseltään epäselvän klonaalisen hematopoieesin ja sydän- ja verisuonitautien yhteyteen

Cardiovascular diseases (CVD) include different disorders of the heart and the blood vessels. They are the leading cause of death globally. In addition to traditional risk factors such as hypertension and smoking, a phenomenon called clonal hematopoiesis of indeterminate potential (CHIP) has been connected to CVD risk. In CHIP, hematopoietic stem cells with driver mutations go through clonal expansion, without causing overt hematological malignancy. It is known that sex affects the risk and development of CVDs, as well as the frequency of CHIP and its mutations, but less is known about how sex influences the association between CHIP and the risk, mechanisms and outcomes of CVDs. The purpose of this study is to find out whether there is evidence of this kind of influence of sex on the association between CHIP and CVD. The method used is systematic literature review carried out according to the PRISMA guidelines. The databases used were PubMed and Web of Science. The initial search resulted in a total of 2,538 individual articles from which 24 articles were included in the final review. These included both cohort-based and experimental studies. In total, 15 studies found some sex-based differences in the association between CHIP and CVD, and two additional articles reported on the effects of estrogen on CHIP. In particular, the CHIP associated gene DNMT3A was found to show sex-specific effects on the risk of various CVDs, for example myocardial infarction and heart failure, as well as increased plaque rupture risk. The proliferation of cells with DNMT3A was also found to be increased by estrogen which might in part explain why it is more common in women and shows female-specific effects. Also some other CHIP mutations showed sex-based differences in CVD risk. In experimental studies sex-based differences in the effects of different CHIP mutations were found, for example, in atherosclerosis development and leukocyte counts. In conclusion, evidence for the influence of sex on the association between CHIP and CVD can be found in the current literature. Sex is a factor that should be taken into consideration when studying the risk and mechanisms of the development of CVD in people with CHIP, and when considering possible clinical implications of CHIP.