Risk of Cardiovascular Disease in Primary Sclerosing Cholangitis

Introduction: Primary sclerosing cholangitis (PSC) is an idiopathic, progressive cholestatic disease without curative options except of liver transplantation. Given the immune mediated nature of disease, there is a concern regarding increased cardiovascular risk in PSC, however studies so far have shown inconsistent results. Thus, we sought to analyze the risk of cardiovascular events in PSC. Methods: We conducted a multicenter, propensity score-matched (PSM) cohort study using the TriNeTx research network. The study group consisted of patients diagnosed with PSC and the control group of patients with chronic liver disease never diagnosed with PSC. The primary outcomes were defined as the first incidence of new-onset arrythmia(atrial fibrillation and flutter, tachycardia, bradycardia, ventricular arrhythmia), composite major adverse cardiovascular events (MACE) (myocardial infarction (MI), ischemic stroke, hemorrhagic stroke, heart failure, ventricular arrhythmia, sudden cardiac death), inflammatory heart disease (pericarditis, myocarditis), ischemic heart disease (acute coronary disease, MI, ischemic cardiomyopathy, angina), cerebrovascular complications (stroke, transient ischemic attack), thrombotic disorders (pulmonary embolism, deep vein and superficial vein thrombosis) and cardiac disorders (non-ischemic cardiomyopathy, cardiac arrest, cardiogenic shock). We performed 1:1 PSM using a greedy nearest-neighbor matching algorithm to account for several cardiovascular risk factors including demographics, metabolic, renal disease as well as psycho-social comorbidities (Table 1). Results: 6 388 patients in the PSC group and 1 314 380 patients in the control group were identified from 2011-2023. Following PSM, the 2 cohorts were relatively balanced (n = 6388 each). Average BMI was lower in the PSC cohort (26.39 ± 5.9 vs 29.98 ± 7.5). Furthermore, PSC patients had lower levels of triglycerides, LDL and Hgb A1c, and conversely higher levels of HDL before and after PSM compared to control. These differences, though statistically significant, were small. Overall, except for an increased risk of arrythmias and thrombotic disorders, the PSC cohort had a significantly decreased risk of cerebrovascular and ischemic heart disease, cardiac disorders, and MACE (Table 1). Conclusion: Despite an increased risk in arrhythmias and thrombotic disorders, PSC patients have a significantly decreased risk of cerebrovascular and ischemic heart disease, cardiac disorders, and major adverse cardiovascular events. Table 1. - Baseline characteristics and cardiovascular outcomes before and after PSM Before Matching After Matching Characteristics PSC Non-PSC OR (95% CI) P value PSC Non-PSC OR (95% CI) P value Age at Index 45.96 ± 18.38 51.11 ± 17.68 < 0.0001 45.96 ± 18.38 45.64 ± 18.53 0.3174 Male 3488 (54.6%) 629786 (47.9%) < 0.0001 3488 (54.6%) 3550 (55.6%) 0.2701 Female 2898 (45.4%) 684386 (52.1%) < 0.0001 2898 (45.4%) 2836 (44.4%) 0.2701 White 4722 (73.9%) 874035 (66.5%) < 0.0001 4722 (73.9%) 4756 (74.5%) 0.4918 Black or African American 740 (11.6%) 129407 (9.8%) < 0.0001 740 (11.6%) 715 (11.2%) 0.4863 Hispanic or Latino 339 (5.3%) 146911 (11.2%) < 0.0001 339 (5.3%) 321 (5.0%) 0.4718 Asian 101 (1.6%) 46222 (3.5%) < 0.0001 101 (1.6%) 100 (1.6%) 0.9433 American Indian or Alaska Native 23 (0.4%) 8379 (0.6%) 0.0054 23 (0.4%) 23 (0.4%) 1 Native Hawaiian or Other Pacific Islander 10 (0.2%) 2031 (0.2%) 0.9673 10 (0.2%) 10 (0.2%) 1 Essential (primary) hypertension 1052 (16.5%) 355226 (27.0%) < 0.0001 1052 (16.5%) 1032 (16.2%) 0.632 Vitamin D deficiency 686 (10.7%) 118522 (9.0%) < 0.0001 686 (10.7%) 621 (9.7%) 0.0577 Hyperlipidemia, unspecified 604 (9.5%) 207869 (15.8%) < 0.0001 604 (9.5%) 575 (9.0%) 0.3754 Depressive episode 553 (8.7%) 153326 (11.7%) < 0.0001 553 (8.7%) 487 (7.6%) 0.0327 Overweight and obesity 526 (8.2%) 221166 (16.8%) < 0.0001 526 (8.2%) 501 (7.8%) 0.4159 Type 2 diabetes mellitus 517 (8.1%) 187878 (14.3%) < 0.0001 517 (8.1%) 500 (7.8%) 0.5785 Sleep disorders 494 (7.7%) 168290 (12.8%) < 0.0001 494 (7.7%) 490 (7.7%) 0.8944 Chronic kidney disease (CKD) 271 (4.2%) 54383 (4.1%) 0.6749 271 (4.2%) 254 (4.0%) 0.4486 Nicotine dependence 255 (4.0%) 140821 (10.7%) < 0.0001 255 (4.0%) 263 (4.1%) 0.7197 Alcohol related disorders 124 (1.9%) 65842 (5.0%) < 0.0001 124 (1.9%) 114 (1.8%) 0.5129 Other chronic obstructive pulmonary disease 75 (1.2%) 41498 (3.2%) < 0.0001 75 (1.2%) 82 (1.3%) 0.574 Problems related to employment and unemployment 25 (0.4%) 6663 (0.5%) 0.1942 25 (0.4%) 13 (0.2%) 0.0512 Problems related to housing and economic circumstances 20 (0.3%) 21594 (1.6%) < 0.0001 20 (0.3%) 38 (0.6%) 0.0178 Problems related to education and literacy 10 (0.2%) 3625 (0.3%) 0.0695 10 (0.2%) 10 (0.2%) 1 Occupational exposure to risk factors 10 (0.2%) 1574 (0.1%) 0.3967 10 (0.2%) 10 (0.2%) 1 Cardiovascular outcomes Cerebrovascular complications 248 (3.9%) 77754 (5.9%) 0.64 (0.57, 0.73) < 0.0001 248 (3.9%) 304 (4.8%) 0.81 (0.68, 0.96) 0.0148 Arrhythmia 957 (15.0%) 189488 (14.4%) 1.05 (0.98, 1.12) 0.1901 957 (15.0%) 876 (13.7%) 1.11 (1, 1.22) 0.0409 Ischemic heart disease 135 (2.1%) 51948 (3.9%) 0.53 (0.44, 0.62) < 0.0001 135 (2.1%) 204 (3.2%) 0.65 (0.53, 0.82) 0.0001 Inflammatory heart disease 104 (1.6%) 20860 (1.6%) 1.03 (0.85, 1.25) 0.7869 104 (1.6%) 116 (1.8%) 0.89 (0.69, 1.17) 0.4144 Other cardiac disorders 222 (3.5%) 74608 (5.7%) 0.6 (0.52, 0.68) < 0.0001 222 (3.5%) 282 (4.4%) 0.78 (0.65, 0.93) 0.0064 Thrombotic disorders 564 (8.8%) 74830 (5.7%) 1.61 (1.47, 1.75) < 0.0001 564 (8.8%) 348 (5.4%) 1.68 (1.46, 1.93) < 0.0001 MACEs 472 (7.4%) 136974 (10.4%) 0.69 (0.62, 0.75) < 0.000 472 (7.4%) 541 (8.5%) 0.86 (0.76, 0.98) 0.0239