An analysis of more than 400,000 participants in the UK Biobank revealed that individuals with constipation exhibited more than twice the risk of major adverse cardiac events compared with those having normal bowel habits, according to findings published in the American Journal of Physiology-Heart and Circulatory Physiology.

The study, led by researchers from Monash University, examined the relationship between constipation and three specific types of major adverse cardiac events (MACE): heart failure (HF), ischemic stroke, and acute coronary syndrome (ACS). The strongest association was found with heart failure, followed by ischemic stroke, and ACS.

Among hypertensive patients specifically, those with comorbid constipation showed higher odds of MACE compared with hypertensive patients without constipation. Survival analysis demonstrated a 34% increased risk of subsequent MACE occurrence in this population, even after adjusting for medications affecting gut motility and traditional cardiovascular risk factors.

Of the 157,414 participants with essential hypertension identified through ICD10 code I10 or self-reported medical history, 8.6% had comorbid constipation. The survival analysis subset comprised 110,524 participants who experienced their first MACE diagnosis after their initial hypertension diagnosis, with 99,608 constipation-free and 10,916 with constipation.

The researchers identified 46,891 (11.5%) individuals who had at least one MACE encounter, including 29,704 cases of ACS, 12,847 cases of ischemic stroke, and 14,099 cases of heart failure. Using ICD10 code K59.0, they detected 23,814 (5.8%) cases of constipation, along with 13,035 laxative users, 20,713 cases of functional constipation, and 3,928 cases of irritable bowel syndrome with constipation (IBS-C).

Significant gender disparities emerged in the data. Constipation showed higher prevalence in females, while MACE demonstrated higher prevalence in males. Individual MACE categories showed similar male predominance: ACS (73.5%), stroke (60.5%), and heart failure (64.7%).

Among constipation cases, 56.6% presented with hypertension, 12.8% with positive smoking status, 17.1% with diabetes, and 34.3% with hypercholesterolemia. Standard modifiable cardiovascular risk factors were more prevalent among individuals with MACE: 75.9% had hypertension, 14.2% were smokers, 23.1% had diabetes, and 61.7% had hypercholesterolemia.

Genetic analysis revealed positive correlations between constipation and MACE subgroups ACS), ischemic stroke, and heart failure. The single nucleotide polymorphism-based heritability of constipation was estimated at approximately 4%.

The study utilized multiple analytical models to validate findings. Model 1 adjusted for age, sex, and body mass index; Model 2 added adjustment for calcium channel blockers; and Model 3 incorporated additional cardiovascular risk factors. The association remained significant across all models, though the strength decreased in Model 3.

Laxative users showed stronger associations with MACE compared to IBS-C and functional constipation. The study noted minimal overlap between these different constipation phenotypes and ICD10 K59 constipation cases.

The researchers acknowledged several study limitations, including a lack of adjustments for physical activity, dietary habits, and mental health variables. Additionally, the analysis was restricted to individuals of European ancestry due to the limited representation of other populations in the UK Biobank.