Metabolic Syndrome: Sex-Related Cardiovascular Risk and Therapeutic Approach

The metabolic syndrome (MetS) is a cluster of risk factors for the development of cardiovascular diseases (CVD) and type 2 diabetes (T2DM). According to several meta-analyses, it has been shown that the cardiovascular (CV) risk conferred by the MetS is higher in women in comparison with men. There are many possible reasons to explain a higher CV risk in women with MetS: the most important differences can be attributed to distribution of central adiposity, lipid profile and hormones, but also differences in platelet biology and biochemistry play an important role.

In this article we performed a research using PubMed database reviewing the evidence in literature (in particular clinical trials and meta-analyses) or lack of evidence/ biased information regarding the distribution by gender of MetS components and associated CV risk and we intended to provide a consequent gender perspective to the treatment of MetS and CV risk.

Twenty-three papers were evaluated searching for sex differences in the prevalence of MetS and CV risk. We also identified fifty-six papers dealing with sex differences in adiposity, insulin resistance and hormonal regulation. In terms of gender-specific expression of MetS in chronic disease we analyzed thirty-one papers focusing the attention on non-alcoholic fatty liver disease, polycystic ovarian syndrome, gestational diabetes mellitus, rheumatoid arthritis and HIV infection. We also evaluated twenty papers focusing on gender differences in platelet biology/reactivity and thirty-three papers on the gender approach in the treatment of MetS. The CV risk conferred by MetS segregates differently according to gender; differences between sexes may depend on the different representation of MetS components, gender-specific genetic, acquired metabolic and hormonal milieu and finally on a differential interaction between known risk factors and genderspecific properties, resulting in different degrees of pathophysiological events eventually leading to atherothrombosis. Regarding a potential sex-related therapeutic approach, even if gender-related differences exist in the pharmacokinetics of drugs for differences in body composition, plasma protein binding, metabolizing enzymes and difference in excretion characteristics, we have to acknowledge that women are under-represented in clinical trials, thus preventing from adequately challenging the efficacy and safety of drugs in this gender.

While ncreasing knowledge exists regarding pathophysiological differences between genders in the prevalence of MetS components as well as in the associated cardiometabolic risk, underrepresentation of women in clinical trials and underutilization of guideline therapy, for instance in women with ischemic heart disease, largely flaw the interpretation of epidemiological and clinical evidence. Efforts should be undertaken to fight the so-called "Yentl syndrome" and to promote gender-specific drug trials, or at least studies where subgroup analyses by gender are pre-specified.