Constipation is associated with an increased risk of major adverse cardiac events in a UK population

Background: Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACE). Understanding what other risk factors contribute to MACE is essential for prevention. Constipation shares common risk factors with hypertension and is associated with an increased risk of several cardiovascular diseases. We hypothesised that constipation is an under-appreciated risk factor for MACE. Methods: We used the population healthcare and genomic data in the UK Biobank (UKBB) (n=408,354) to study the contribution of constipation (ICD-10 K59.0) to the risk of MACE, defined by any episode of acute coronary syndrome (ACS), ischemic stroke and heart failure (HF). Analyses were controlled for traditional cardiovascular risk factors. We also assessed genetic correlations (r g ) between constipation and MACE. Results: Constipation cases (N=23,814) exhibited significantly higher risk of MACE compared to those with normal bowel habits (OR=2.15, P<1.00×10 -300 ). Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR=2.72, P<1.00×10 -300 ), ischemic stroke (OR=2.36, P=2.02×10 -230 ), and ACS (OR=1.62, P=5.82×10 -113 ). In comparison with constipation-free hypertensive patients, hypertensives with constipation showed significantly higher odds of MACE (OR=1.68, P=1.05×10 -136 ) and a 34% increased risk of MACE occurrence (P=2.3×10 -50 ) after adjustment for medications that affect gut motility and other traditional cardiovascular risk factors. Finally, we detected positive genetic correlations between constipation and MACE subgroups ACS (r g =0.27, P=2.12×10 -6 ), ischemic stroke (r g =0.23, P=0.011), and HF (r g =0.21, P=0.0062). Conclusion: We identified constipation as a potential risk factor independently associated with higher MACE prevalence. These findings warrant further studies on their causal relationship and identification of pathophysiological mechanisms.