Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature

Pucci, Giacomo; Alcidi, Riccardo; Tap, Lisanne; Battista, Francesca; Mattace-Raso, Francesco; Schillaci, Giuseppe

doi:10.1016/j.phrs.2017.03.008

Cited by 349 publications

(295 citation statements)

References 79 publications

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“…21 These distinctions could also have direct implications for the results of the study by Sullivan et al 7 because there is some suggestion that sex may drive heart disease pathways associated with factors such as abdominal obesity and insulin-resistance, whereas gender my drive heart disease through factors such as psychology distress and acute stress. 22 As such, how much of the sex difference seen could actually be attributable to gender or how much more might gender be able to explain the variability of stress responses? As with the arguments above, answers to these questions should ultimately lead us to better tailored medical care.…”

Section: See Accompanying Article On Page 473mentioning

confidence: 99%

The Importance of Sex in the Stress–Heart Disease Relationship and the Potential Contribution of Gender to Future Research

Bacon

2018

ATVB

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We now have numerous studies that have linked increased levels of negative emotions and stress with the development and progression of cardiovascular disease-a relationship that seems to be sex specific in its pattern of outcomes. 1,2 However, the mechanisms of these relationships are still a source of much debate. One of the strongest potential pathways linking acute psychological stress with worse outcomes is through mental stress-induced myocardial ischemia (MSIMI).3 Though there is a large overlap (ca. 70%) in individuals who demonstrate both MSIMI and more common (ie, exercise or pharmacological) stress-induced ischemia, 4 these seem to be distinctly different entities. Firstly, it would seem that more individuals are likely to have MSIMI only than exercise/pharmacological stress-induced ischemia only (20% versus 10%).5 Furthermore, the profiles and potential mechanistic factors of those at risk for MSIMI compared with exercise/pharmacological stress-induced ischemia are different. For example, those individuals who exhibit MSIMI are more likely to be women, have greater microvascular disease, have poorer left ventricular dysfunction, and display endothelial dysfunction, whereas exercise/pharmacological stress-induced ischemia is generally associated with men and those with larger and more diffuse coronary artery plaque. [4][5][6] Though there are sex differences in the rates of presentations of both MSIMI and exercise/pharmacological stress-induced ischemia, both men and women do exhibit both of these forms of ischemia. However, we do not know if the mechanistic factors that underlie these stress-induced ischemia differ by sex; for example, does MSIMI in women differ from MSIMI in men? Understanding these processes can ultimately help in the development of better tailored diagnostic procedures and interventions to treat cardiovascular disease. See accompanying article on page 473The article by Sullivan et al 7 provides some important initial insights into sex differences in the potential mechanisms driving MSIMI. This secondary analysis of 678 (25% women) patients in the MIPS study (Mental Stress Ischemia Mechanisms and Prognosis) evaluated mental stress (public speaking)-induced vascular and hemodynamic responses. The authors found that MSIMI was generally driven by peripheral vasoconstriction in women compared with increased hemodynamic workload in men, results that were independent of exercise/pharmacological stress-induced ischemia. These results suggest that men with MSIMI are effectively cardiac stress reactors, with increased myocardial oxygen demands, and women with MSIMI are more likely to be vascular reactors, with greater endothelial driven increases in vascular resistance (which leads to increased left ventricular afterload and dysfunction).8 However, the article by Sullivan et al does only provide initial insights, and there is a great deal of further information that we need. For example, building a more complex map of MSIMI, to include additional measures of the autonomic nervous system, the...

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Section: See Accompanying Article On Page 473mentioning

confidence: 99%

The Importance of Sex in the Stress–Heart Disease Relationship and the Potential Contribution of Gender to Future Research

Bacon

2018

ATVB

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“…In these ways, endothelial dysfunction contributes to the development of atherosclerosis and progression to plaque rupture and thrombosis, the cause of cardiovascular ischemia, which is the leading cause of death in both sexes 1, 2. Although premenopausal women are protected from CVD relative to men, this protection is attenuated in obese young women, particularly those with metabolic syndrome or diabetes mellitus,8 yet the molecular mechanisms remain unknown.…”

Section: Introductionmentioning

confidence: 99%

Sex‐Specific Mechanisms of Resistance Vessel Endothelial Dysfunction Induced by Cardiometabolic Risk Factors

Davel

Lü

Moss

et al. 2018

JAHA

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BackgroundThe incidence of obesity is rising, particularly among women. Microvascular dysfunction is more common with female sex, obesity, and hyperlipidemia and predicts adverse cardiovascular outcomes, but the molecular mechanisms are unclear. Because obesity is associated with mineralocorticoid receptor (MR) activation, we tested the hypothesis that MR in endothelial cells contribute to sex differences in resistance vessel dysfunction in response to cardiometabolic risk factors.Methods and ResultsMale and female endothelial cell–specific MR knockout mice and MR‐intact littermates were randomized to high‐fat‐diet–induced obesity or obesity with hyperlipidemia induced by adeno‐associated virus–based vector targeting transfer of the mutant stable form (DY mutation) of the human PCSK9 (proprotein convertase subtilisin/kexin type 9) gene and compared with control diet. Female but not male mice were sensitive to obesity‐induced endothelial dysfunction, whereas endothelial function was impaired in obese hyperlipidemic males and females. In males, obesity or hyperlipidemia decreased the nitric oxide component of vasodilation without altering superoxide production or endothelial nitric oxide synthase expression or phosphorylation. Decreased nitric oxide content in obese males was overcome by enhanced endothelium‐derived hyperpolarization–mediated relaxation along with increased SK3 expression. Conversely, in females, endothelium‐derived hyperpolarization was significantly impaired by obesity with lower IK1 expression and by hyperlipidemia with lower IK1 and SK3 expression, loss of H2O2‐mediated vasodilation, and increased superoxide production. Endothelial cell–MR deletion prevented endothelial dysfunction induced by risk factors only in females. Rather than restoring endothelium‐derived hyperpolarization in females, endothelial cell–MR deletion enhanced nitric oxide and prevented hyperlipidemia‐induced oxidative stress.ConclusionsThese data reveal distinct mechanisms driving resistance vessel dysfunction in males versus females and suggest that personalized treatments are needed to prevent the progression of vascular disease in the setting of obesity, depending on both the sex and the metabolic profile of each patient.

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“…For example, studies in different ethnic groups have suggested that age related increases in the prevalence of metabolic syndrome are greater in women then in men (see review ref. 30). Similarly, impaired glucose tolerance has been reported to be more prevalent in older women than men, although impaired fasting glycaemia more prevalent in men 31 .…”

Section: Discussionmentioning

confidence: 99%

[P4–134]: Insulin Resistance Is Associated With Reductions in Specific Cognitive Domains and Increases in CSF Tau in Cognitively Normal Adults

Laws

Gaskin

Woodfield

et al. 2017

Alzheimer's & Dementia

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Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstratesEpidemiological studies indicate that Type 2 diabetes (T2D) is associated with an increased risk of dementia [1][2][3][4][5] . Clinical studies using cross-sectional designs support this association by showing that cognition is worse in patients with T2D as compared to matched controls without T2D 6,7 . Furthermore, studies of structural magnetic resonance imaging (MRI) show that in T2D cognitive impairment is associated with greater levels of vascular

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Sex- and gender-related prevalence, cardiovascular risk and therapeutic approach in metabolic syndrome: A review of the literature

Cited by 349 publications

References 79 publications

The Importance of Sex in the Stress–Heart Disease Relationship and the Potential Contribution of Gender to Future Research

The Importance of Sex in the Stress–Heart Disease Relationship and the Potential Contribution of Gender to Future Research

Sex‐Specific Mechanisms of Resistance Vessel Endothelial Dysfunction Induced by Cardiometabolic Risk Factors

[P4–134]: Insulin Resistance Is Associated With Reductions in Specific Cognitive Domains and Increases in CSF Tau in Cognitively Normal Adults

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