Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System

Ueda, Kazutaka; Fukuma, Nobuaki; Adachi, Yusuke; Numata, Genri; Tokiwa, Hiroyuki; Toyoda, Masahiko; Otani, Amato; Hashimoto, Masaki; Liu, Pang‐Yen; Takimoto, Eiki

doi:10.3389/fphys.2021.738218

Cited by 29 publications

(29 citation statements)

References 101 publications

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“…Similarly, an additive effect of NFS and PCSK9 on cardiovascular events was found in men. Hormones such as estrogen seem to play a critical role in such a phenomenon [ 41 ]. More studies will be conducted to identify potential sex-related differences in the association of PCSK9 and NFS levels with cardiovascular risk.…”

Section: Discussionmentioning

confidence: 99%

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

et al. 2022

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Background The risk of liver fibrosis in non-alcoholic fatty liver disease (NAFLD) can be easily evaluated by noninvasive scoring systems, of which the NAFLD fibrosis score (NFS) is the most commonly used. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a new predictor of cardiovascular events, has been reported to be associated with cardiovascular outcomes and NAFLD. However, the relationship of NFS with PCSK9 and their prognostic abilities in cardiovascular risks are unknown. Methods A total of 2008 hospitalized subjects who had chest pain without lipid-lowering therapy were consecutively included. Baseline clinical data were collected, and the NFS was calculated. The circulating PCSK9 concentration was determined by enzyme immunoassay. The major adverse cardiovascular event (MACE) occurrences were recorded in the follow-up period. Associations of PCSK9 concentration with NFS were examined. All of the participants were categorized into three groups according to NFS levels and were further stratified by PCSK9 tertiles to evaluate the MACEs. Results 158 (7.87%) MACEs were observed during a mean of 3.2 years of follow-up. NFS levels were independently related to higher PCSK9 levels according to multivariable linear regression analysis. Furthermore, elevated PCSK9 and NFS concentrations were respectively associated with increased MACE incidence in multivariable Cox regression models. When combining NFS status with PCSK9 tertiles as a stratifying factor, patients with intermediate-high NFS and high PCSK9 levels had higher risks of events than those with low NFS and low PCSK9 levels. Conclusions This study revealed for the first time that NFS is positively related to PCSK9 and that the combination of NFS and PCSK9 greatly increased the risk of MACEs in patients with chest pain, providing a potential link between NFS and PCSK9 for predicting cardiovascular events.

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Section: Discussionmentioning

confidence: 99%

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

et al. 2022

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“…Moreover, early-onset menopause leads to premature CAD [ 131 ]. Estrogens have a protective effect on the development of CAD [ 58 , 132 ]. On the contrary, women with an early onset of CAD (<35 years) are more likely to experience early menopause.…”

Section: Cardiovascular Gender-specific Risk Factorsmentioning

confidence: 99%

Update on Management of Cardiovascular Diseases in Women

Lucà¹,

Abrignani

Parrini

et al. 2022

JCM

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Cardiovascular diseases (CVD) have a lower prevalence in women than men; although, a higher mortality rate and a poorer prognosis are more common in women. However, there is a misperception of CVD female risk since women have commonly been considered more protected so that the real threat is vastly underestimated. Consequently, female patients are more likely to be treated less aggressively, and a lower rate of diagnostic and interventional procedures is performed in women than in men. In addition, there are substantial sex differences in CVD, so different strategies are needed. This review aims to evaluate the main gender-specific approaches in CVD.

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“…It is well recognized that menopausal women undergo CVD more than men of the same age [ 111 ]. The causes for this sex/gender difference remain a subject of debate but seem likely to be linked to the beneficial effects of sex hormones, particularly estrogens (Es) [ 7 , 8 , 9 , 10 ]. As age progresses, during and after menopause, there is a cessation of ovarian follicle development followed by dramatic declines in E levels, especially 17β-estradiol (E2), the most potent and active metabolite in humans.…”

Section: Estrogens and Cvdmentioning

confidence: 99%

“…In animals and humans with cardiac disease, females display lower mortality, less severe disease phenotype, and faster cardiac repair than their male counterparts [ 3 , 4 , 5 , 6 ]. This difference has been primarily attributed to sex hormones such as estrogens (Es) [ 7 , 8 , 9 , 10 ]. Es are undeniably protective in women, and their decline during and after menopause coincides with increased CV risk and HF development [ 11 ].…”

Section: Introductionmentioning

confidence: 99%

Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

Arosio

Corbi

Davinelli

et al. 2022

IJMS

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The medical community recognizes sex-related differences in pathophysiology and cardiovascular disease outcomes (CVD), culminating with heart failure. In general, pre-menopausal women tend to have a better prognosis than men. Explaining why this occurs is not a simple matter. For decades, sex hormones like estrogens (Es) have been identified as one of the leading factors driving these sex differences. Indeed, Es seem protective in women as their decline, during and after menopause, coincides with an increased CV risk and HF development. However, clinical trials demonstrated that E replacement in post-menopause women results in adverse cardiac events and increased risk of breast cancer. Thus, a deeper understanding of E-related mechanisms is needed to provide a vital gateway toward better CVD prevention and treatment in women. Of note, sphingolipids (SLs) and their metabolism are strictly related to E activities. Among the SLs, ceramide and sphingosine 1-phosphate play essential roles in mammalian physiology, particularly in the CV system, and appear differently modulated in males and females. In keeping with this view, here we explore the most recent experimental and clinical observations about the role of E and SL metabolism, emphasizing how these factors impact the CV system.

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Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System

Cited by 29 publications

References 101 publications

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

NAFLD fibrosis score is correlated with PCSK9 and improves outcome prediction of PCSK9 in patients with chest pain: a cohort study

Update on Management of Cardiovascular Diseases in Women

Sex Differences in Cardiovascular Diseases: A Matter of Estrogens, Ceramides, and Sphingosine 1-Phosphate

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