Constipation and risk of death and cardiovascular events

Abstract

Background and aims: Constipation is one of the most frequent symptoms encountered in daily clinical practice and is implicated in the development of atherosclerosis, potentially through altered gut microbiota. However, little is known about its association with incident cardiovascular events.

Methods: In a nationally representative cohort of 3,359,653 US veterans with an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m² between October 1, 2004 and September 30, 2006 (baseline period), with follow-up through 2013, we examined the association of constipation status (absence or presence; defined using diagnostic codes and laxative use) and laxative use (none, one, or ≥2 types of laxatives) with all-cause mortality, incident coronary heart disease (CHD), and incident ischemic stroke.

Results: Among 3,359,653 patients, 237,855 (7.1%) were identified as having constipation. After multivariable adjustments for demographics, prevalent comorbidities, medications, and socioeconomic status, patients with (versus without) constipation had 12% higher all-cause mortality (hazard ratio [HR], 1.12; 95% CI, 1.11-1.13), 11% higher incidence of CHD (HR, 1.11; 95% CI, 1.08-1.14), and 19% higher incidence of ischemic stroke (HR, 1.19; 95% CI, 1.15-1.22). Patients with one and ≥2 (versus none) types of laxatives experienced a similarly higher risk of all-cause mortality (HRs [95% CI], 1.15 [1.13-1.16] and 1.14 [1.12-1.15], respectively), incident CHD (HRs [95% CI], 1.11 [1.07-1.15] and 1.10 [1.05-1.15], respectively) and incident ischemic stroke (HRs [95% CI], 1.19 [1.14-1.23] and 1.21 [1.16-1.26], respectively).

Conclusions: Constipation status and laxative use are independently associated with higher risk of all-cause mortality and incident CHD and ischemic stroke.

Keywords: Constipation; Coronary heart disease; Laxatives; Mortality; Stroke.

Figure 1.

Kaplan-Meier cumulative-event curves for all-cause mortality according to (A) constipation status and (B) laxative use in the overall cohort The lines represent (A) patients without (dashed line) and with (solid line) constipation, and (B) those with no laxatives (dotted line) and with one (dashed line) or ≥2 (solid line) types of laxatives. Both log-rank p values <0.001.

Figure 1.

Kaplan-Meier cumulative-event curves for all-cause mortality according to (A) constipation status and (B) laxative use in the overall cohort The lines represent (A) patients without (dashed line) and with (solid line) constipation, and (B) those with no laxatives (dotted line) and with one (dashed line) or ≥2 (solid line) types of laxatives. Both log-rank p values <0.001.

Figure 2.

Hazard ratios and 95% confidence intervals of (A) all-cause mortality, (B) incident CHD, and (C) incident stroke associated with the presence (vs. absence) of constipation in the overall cohort. Models represent hazard ratios after adjustment for age (model 1); age plus gender, race, and baseline eGFR (model 2); model 2 variables plus comorbidities (diabetes mellitus, hypertension, coronary heart disease, congestive heart failure, cerebrovascular disease, peripheral arterial disease, peptic ulcer disease, rheumatic disease, malignancy, dementia, Parkinson’s disease, depression, liver disease, chronic lung disease, human immunodeficiency virus/acquired immunodeficiency syndrome, and bowel disorders) and Charlson comorbidity index (model 3); model 3 plus baseline body mass index, systolic blood pressure, diastolic blood pressure, and total cholesterol (model 4); model 4 plus socioeconomic parameters (mean per capita income, marital status, service connectedness, housing stress, low education, low employment, persistent poverty), number of VA healthcare encounters, cumulative length of hospitalization, receipt of influenza vaccination(s), each patient’s VA healthcare region, and use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, calcium channel blockers, diuretics, statins, antidepressants, non-opioid analgesics, opioids, antihistamines, anticholinergics, antiarrhythmics, anticoagulants, antipsychotics, anti-Parkinson drugs, antacids, anticonvulsants, alkylating agents, and oral iron supplements (model 5). CHD = coronary heart disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; VA = veterans affairs.

Figure 3.

Hazard ratios and 95% confidence intervals of (A) all-cause mortality, (B) incident CHD, and (C) incident stroke associated with laxative use* in the overall cohort. *Patients with one (blank symbols) or ≥2 (filled symbols) types of laxatives compared with those with no laxatives (reference). Models represent hazard ratios after adjustment for age (model 1); age plus gender, race, and baseline eGFR (model 2); model 2 variables plus comorbidities (diabetes mellitus, hypertension, coronary heart disease, congestive heart failure, cerebrovascular disease, peripheral arterial disease, peptic ulcer disease, rheumatic disease, malignancy, dementia, Parkinson’s disease, depression, liver disease, chronic lung disease, human immunodeficiency virus/acquired immunodeficiency syndrome, and bowel disorders) and Charlson comorbidity index (model 3); model 3 plus baseline body mass index, systolic blood pressure, diastolic blood pressure, and total cholesterol (model 4); model 4 plus socioeconomic parameters (mean per capita income, marital status, service connectedness, housing stress, low education, low employment, persistent poverty), number of VA healthcare encounters, cumulative length of hospitalization, receipt of influenza vaccination(s), each patient’s VA healthcare region, and use of angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers, calcium channel blockers, diuretics, statins, antidepressants, non-opioid analgesics, opioids, antihistamines, anticholinergics, antiarrhythmics, anticoagulants, antipsychotics, anti-Parkinson drugs, antacids, anticonvulsants, alkylating agents, and oral iron supplements (model 5). CHD = coronary heart disease; CI = confidence interval; eGFR = estimated glomerular filtration rate; VA = veterans affairs.