Metabolic syndrome, the cluster of abdominal obesity, high blood pressure, elevated blood glucose, high triglycerides and low HDL cholesterol, increases the risk of developing atrial fibrillation in both men and women, but the size and timing of that risk appear to differ sharply between the sexes. That is the central conclusion of a narrative mini review published in Frontiers in Cardiovascular Medicine by a team of Italian researchers led by Stefano Bonapace of IRCCS Sacro Cuore Don Calabria in Negrar di Valpolicella. Drawing together cohort studies and meta-analyses from Asian and Western populations, the authors argue that sex-specific biology, particularly sex hormones and their effects on fat distribution, helps explain why men tend to develop the arrhythmia earlier while women catch up steeply after menopause.
Atrial fibrillation is the most common sustained arrhythmia worldwide, affecting between 2 and 4 percent of adults, and it substantially raises the risk of ischemic stroke, congestive heart failure and death. Prevalence is expected to roughly double in coming years as populations age and diagnosis improves. The review notes that metabolic syndrome, diagnosed when at least three of five abnormalities are present under the National Cholesterol Education Program Adult Treatment Panel III criteria, is rising in parallel with atrial fibrillation prevalence, and epidemiological studies consistently link the two conditions.
Quantitatively, the review reports that metabolic syndrome increases the risk of incident atrial fibrillation by approximately 1.4- to 1.9-fold. A meta-analysis of six observational studies by Zeng and colleagues found a roughly 1.6-fold increased risk, with increased blood pressure the strongest individual component (hazard ratio 1.56), followed by abdominal obesity (1.37), elevated blood glucose (1.18) and low HDL cholesterol (1.18). In the large South Korean National Health Insurance cohort of about 22.9 million middle-aged adults studied by Choe and colleagues, the hazard ratio for incident atrial fibrillation with metabolic syndrome was 1.38 after adjustment, and people with all five components had a nearly 2.2-fold higher risk than those with none.
The sex gap is striking in the individual cohorts. In the Japanese study by Watanabe and colleagues, which followed 28,449 middle-aged people without baseline atrial fibrillation for a mean of 4.5 years, new-onset atrial fibrillation occurred at a rate of 4.1 per 1,000 person-years in men versus 1.3 in women. Metabolic syndrome itself raised risk by nearly 1.9-fold under the NCEP-ATP III definition and 1.6-fold under the AHA/NHLBI definition, with obesity (hazard ratio 1.64) and raised blood pressure (1.69) contributing most, while triglycerides showed no significant association. In a nationwide Korean cohort of roughly 7.8 million adults aged 30 to 69 studied by Kwon and colleagues, pre-metabolic syndrome conferred a 1.4-fold higher risk and full metabolic syndrome a 1.7-fold higher risk, with men showing higher incidence across every age decade and women displaying a sharp rise after age 60.
Not every study finds a sex difference, and the review is careful to note the exceptions. A retrospective cohort of 21,981 Korean men with a mean age of 46, studied by Kim and colleagues, found a hazard ratio of 1.57 for atrial fibrillation with metabolic syndrome, with abdominal obesity the only component remaining significant after multivariable adjustment, but the cohort was male-only by design. In a hypertensive population of 15,075 non-diabetic patients studied by Vyssoulis and colleagues, metabolic syndrome was associated with atrial fibrillation regardless of which of five definitions was used, yet no association between sex and atrial fibrillation emerged. Apart from these two studies, the review states, all others examined observed a differential impact of sex on incident atrial fibrillation risk.
European cohorts reinforce the pattern. In the BiomarCaRE pooled analysis of 79,793 people without atrial fibrillation followed for a median of 12.6 years, Magnussen and colleagues recorded new atrial fibrillation in 4.4 percent of women and 6.4 percent of men, with cumulative incidence rising markedly after age 50 in men and after age 60 in women before converging at older ages. The association between body mass index and atrial fibrillation was stronger in men (hazard ratio 1.31 per standard deviation) than in women (1.18). In the Danish Diet, Cancer, and Health Study of 47,589 middle-aged adults, the hazard ratio for atrial fibrillation was 1.75 in men and 1.39 in women, and obesity carried a hazard ratio of 2.35 in men versus 1.99 in women, suggesting a sex-specific interaction between body mass index and the arrhythmia. A 15-year follow-up of the Busselton cohort in Western Australia likewise found the effect of body mass index on atrial fibrillation risk stronger in men.
The review then turns to mechanisms, which remain hypothetical rather than proven. The authors propose that sex hormones shape fat distribution, lipid metabolism, insulin sensitivity and inflammation in ways that create distinct metabolic risk profiles. Estrogens favour storage of subcutaneous fat around the hips and thighs, the so-called gynoid pattern, which is less metabolically active and less likely to drive insulin resistance and low-grade inflammation. Estrogens also support more favourable lipid profiles, raising HDL cholesterol and lowering LDL cholesterol and triglycerides, and improve insulin sensitivity, which the authors link to the lower atrial fibrillation incidence seen in younger women.
Men, by contrast, tend to accumulate visceral fat around the abdomen and internal organs under the influence of testosterone. Visceral adipose tissue releases pro-inflammatory cytokines and free fatty acids that worsen insulin resistance and promote atherogenic dyslipidemia, creating an earlier metabolic derangement that may help explain why men develop atrial fibrillation at younger ages. Ageing complicates the picture in both sexes: after menopause, declining estrogen shifts women toward central adiposity, worsened lipids and insulin resistance, narrowing the incidence gap, while in older men declining testosterone is linked to lower muscle mass and increased visceral fat. In men aged 80 and older from the Framingham Heart Study, Magnani and colleagues reported that a one-standard-deviation decrease in plasma testosterone was associated with a hazard ratio of 3.53 for atrial fibrillation, an association not evident at younger ages. Baek and colleagues found the age-adjusted hazard ratio for new-onset atrial fibrillation with abdominal obesity was 1.44 in men versus 1.23 in women.
The review also highlights differences in autonomic regulation and related metabolic liver disease. Men with metabolic syndrome may experience more severe autonomic dysfunction dominated by sympathetic nervous system activity, and studies cited in the review found plasma adrenaline rose more in obese men than in obese women, while noradrenaline spillover in healthy older men was higher than in women and positively related to waist circumference. A general preponderance of sympathetic-mediated responses in men and parasympathetic-mediated responses in women may further modulate atrial fibrillation risk. The authors add that metabolic dysfunction-associated steatotic liver disease, which is closely tied to metabolic syndrome and to increased atrial fibrillation risk, is more prevalent in men and rises in women after menopause, fitting the same sex-specific pattern.
The authors conclude that while metabolic syndrome raises atrial fibrillation risk in both sexes, the magnitude, timing and underlying mechanisms of that risk differ between men and women, and they call for better integration of sex-specific biological pathways into prevention strategies. As a narrative mini review, the work synthesises existing observational studies rather than presenting new clinical trial data, and the authors themselves acknowledge that the causes of the sex differences remain unclear, with both biological and psychosocial factors, including smoking, alcohol consumption, diet and physical activity, potentially contributing. Even so, the converging evidence across millions of cohort participants points to a consistent message: metabolic health and sex interact in determining who develops the world’s most common sustained arrhythmia, and when.
Subject of Research: Sex differences in atrial fibrillation incidence among people with metabolic syndrome
Article Title: Sex differences in atrial fibrillation incidence among individuals with metabolic syndrome: a narrative mini review
Article References: Bonapace, S., Molon, G., Tosi, P., Campopiano, E., Costa, A., Pepe, A., Morandin, R., Marinelli, A., Targher, G., & Mantovani, A. (2026). Sex differences in atrial fibrillation incidence among individuals with metabolic syndrome: a narrative mini review. Frontiers in Cardiovascular Medicine, 13, 1969128. https://doi.org/10.3389/fcvm.2026.1969128
Image Credits: AI Generated
DOI: 10.3389/fcvm.2026.1969128
Keywords: atrial fibrillation, metabolic syndrome, sex differences, menopause, estrogen, testosterone, visceral fat, obesity, blood pressure, insulin resistance, epidemiology, autonomic nervous system
News Source: Ophelia Keating. (October 28, 2026). Metabolic syndrome raises atrial fibrillation risk differently in men and women, review finds. Scienmag.
