Sex, gut microbiome, and cardiovascular disease risk

Alexander C. Razavi; Kaitlin S. Potts; Tanika N. Kelly; Lydia A. Bazzano

doi:10.1186/s13293-019-0240-z

Biology of Sex Differences

Table 1 Sexual dimorphism in four main cardiovascular disease risk factors

From: Sex, gut microbiome, and cardiovascular disease risk

CVD risk factor	Men	Women	Evidence/potential mechanisms
Impaired glucose regulation^A	↑ Incidence of impaired fasting glucose ↑ Incidence of diabetes at earlier ages ↓ Insulin sensitivity	↑ Incidence of impaired glucose tolerance ↓ Incidence of diabetes ↑ Insulin sensitivity	Estrogens may confer a protective effect on insulin-glucose homeostasis [172,173,174,175,176,177,178]: - Reduction in inflammation, reactive oxygen species, hepatic glucose production, and central and visceral adiposity. - Improves glucose uptake by skeletal muscle via activation of PPAR-γ. Testosterone appears to exhibit a U-shaped association with insulin resistance [179,180,181,182,183]: - Excess testosterone in both sexes is associated with dysglycemia and inhibits myocyte, adipocyte insulin in women. - Testosterone associates with reduced visceral and central adiposity, as well as decreased waist-to-hip ratio in men.
Dyslipidemia^B	↓ HDL-C ↑ LDL-C ↑ VLDL ↑ Total plasma TG ↑ FFA oxidation at rest	↑ HDL-C ↓ LDL-C ↓ VLDL ↓ Total plasma TG ↑ FFA storage at rest	Sexual dimorphism is observed in lipid profiles of premenopausal women compared to men [184,185,186,187]
Hypertension^C	Younger ages [118, 188,189,190] ↑ Systolic BP ↑ Incident hypertension ↓ Salt sensitivity Older ages ↓ Incident hypertension All ages ↑ Diastolic BP ↓ Survival with hypertension	Younger ages ↓ Systolic BP ↓ Incident hypertension ↑ Salt sensitivity Older ages (postmenopausal) ↑ Incident hypertension All ages ↓ Diastolic BP ↑ Survival with hypertension	Endogenous estrogen has a BP lowering effect [118, 191,192,193,194]. - Possible mechanisms include RAAS and endothelin system, oxidative stress, nitric oxide production, and salt sensitivity. Androgens (testosterone) have pro-hypertensive properties. - Possible mechanisms include blunting of the pressure-natriuresis relationship, RAAS, and oxidative stress.
Obesity^D	↓ Obesity [195] ↑ Lean tissue; ↓ Total fat ↑ Visceral adipose tissue	↑ Obesity [195] ↓ Lean tissue; ↑ Total fat ↑ Subcutaneous adipose tissue	Estrogen and androgens impact energy utilization, storage, and fat distribution [196,197,198,199].

^ABroad category of prediabetic syndromes, including impaired fasting glucose (WHO criteria, > 110 mg/dL; ADA criteria, > 100 mg/dL) as well as impaired glucose tolerance, a condition in which a given concentration of insulin, endogenous or exogenous, is accompanied by an inadequate glucose response
^BAn elevation in circulating total cholesterol, low-density lipoprotein, high-density lipoprotein, and/or triglycerides
^CDefined by ACC/AHA 2017 guidelines: systolic blood pressure ≥ 130 mmHg or diastolic blood pressure ≥ 80 mmHg
^DDefined by a body mass index ≥ 30 kg/m²
BP blood pressure, FFA free fatty acids, HDL-C high-density lipoprotein cholesterol, LDL-C low-density lipoprotein cholesterol, PPAR-γ peroxisome proliferator-activator gamma, RAAS renin-angiotensin-aldosterone system, VLDL-C very low-density lipoprotein cholesterol

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