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

Traditional cardiovascular risk factors, including hypertension, only explain part of major adverse cardiac events (MACEs). 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 hypothesized that constipation is an underappreciated risk factor for MACE. We used the population healthcare and genomic data in the UK Biobank (<i>n</i> = 408,354) to study the contribution of constipation (ICD10 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 (<i>r</i>_g) between constipation and MACE. Constipation cases (<i>n =</i> 23,814) exhibited a significantly higher risk of MACE compared with those with normal bowel habits [odds ratio (OR) = 2.15, <i>P</i> < 1.00 × 10^-300]. Constipation was also significantly associated with individual MACE subgroups, in order: HF (OR = 2.72, <i>P</i> < 1.00 × 10^-300), ischemic stroke (OR = 2.36, <i>P</i> = 2.02 × 10^-230), and ACS (OR = 1.62, <i>P</i> = 5.82 × 10^-113). In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE (OR = 1.68, <i>P</i> = 1.05 × 10^-136) and a 34% increased risk of MACE occurrence (<i>P</i> = 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 (<i>r</i>_g = 0.27, <i>P</i> = 2.12 × 10^-6), ischemic stroke (<i>r</i>_g = 0.23, <i>P</i> = 0.011), and HF (<i>r</i>_g = 0.21, <i>P</i> = 0.0062). 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.<b>NEW & NOTEWORTHY</b> Analyzing 408,354 participants of the UK Biobank, we show that constipation cases exhibited a significantly higher risk of major adverse cardiac events (MACEs) than those with regular bowel habits. In comparison with patients with constipation-free hypertension, patients with hypertension with constipation showed significantly higher odds of MACE and a 34% increased risk of subsequent MACE occurrence. Finally, we detected positive genetic correlations between constipation and MACE. This association holds potential for therapeutic exploitation and prevention based on individuals' risk assessment.