Systematic Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2019; 25(44): 6561-6570
Published online Nov 28, 2019. doi: 10.3748/wjg.v25.i44.6561
Chronic pancreatitis and the heart disease: Still terra incognita?
Sara Nikolic, Ana Dugic, Corinna Steiner, Apostolos V Tsolakis, Ida Marie Haugen Löfman, J-Matthias Löhr, Miroslav Vujasinovic
Sara Nikolic, Miroslav Vujasinovic, Department of Medicine Huddinge, Karolinska Institute, Stockholm 14183, Sweden
Sara Nikolic, Department of Gastroenterology, Division of Internal Medicine, University Medical Centre Maribor, Maribor 2000, Slovenia
Ana Dugic, Department of Medicine, Klinikum Bayreuth, Bayreuth 95445, Germany
Corinna Steiner, Apostolos V Tsolakis, J-Matthias Löhr, Miroslav Vujasinovic, Department for Digestive Diseases, Karolinska University Hospital, Stockholm 14186, Sweden
Apostolos V Tsolakis, Department of Oncology and Pathology, Karolinska Institute, Stockholm 17176, Sweden
Apostolos V Tsolakis, Cancer Centre Karolinska, CCK, Karolinska University Hospital, Stockholm 17176, Sweden
Ida Marie Haugen Löfman, Unit of Cardiology, Heart and Vascular Theme, Karolinska University Hospital Huddinge, Stockholm 14186, Sweden
Ida Marie Haugen Löfman, Department of Medicine Solna, Karolinska Institute, Stockholm 17176, Sweden
J-Matthias Löhr, Department of Clinical Science, Intervention, and Technology (CLINTEC), Karolinska Institute, Stockholm 17176, Sweden
Author contributions: Nikolic S and Vujasinovic M contributed to the conception and design of the study, literature review and selection of the eligible studies, analysis and interpretation of data and drafting of the manuscript; Dugic A contributed to literature review, selection of the eligible studies, analysis of data, and critical revision and editing; Steiner C , Tsolakis AV, Haugen Löfman IM, contributed to critical revision and editing; Löhr JM contributed to literature review and analysis, drafting of the manuscript and critical revision and editing.
Conflict-of-interest statement: Vujasinovic M and Löhr JM have worked as speakers for Mylan and Abbott Laboratories. Nikolic S has worked as a speaker for Mylan, Krka, Servier and Ferring. Authors declare no potential conflicts of interest and no financial support regarding presenting the manuscript.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Miroslav Vujasinovic, MD, PhD, Doctor, Department for Digestive Diseases, Karolinska University Hospital, Hälsovägen 11, Stockholm 14186, Sweden.
Telephone: +46-72-4694938
Received: October 4, 2019
Peer-review started: October 4, 2019
First decision: November 4, 2019
Revised: November 8, 2019
Accepted: November 16, 2019
Article in press: November 16, 2019
Published online: November 28, 2019
Research background

Chronic pancreatitis (CP) is a persistent inflammation of the pancreas and with time fibrosis develops. Pancreatic exocrine insufficiency (PEI) due to loss of intact pancreatic acinar cells, represents one of the most frequent complications of CP. Chronic heart failure is a complex clinical syndrome where the heart is incapable of maintaining a cardiac output that is adequate to meet human metabolic requirements. Association between CP and heart disease was reported.

Research motivation

Despite sharing risk factors for atherosclerosis among patients with cardiovascular diseases (CVD) and CP, it has been suggested that CP may be an independent risk factor for development of CVD. At the same time, it seems that congestive heart failure (CHF) and CP share the responsibility for the development of important clinical entities such as sarcopenia, cachexia and malnutrition consequences of cardiac cachexia and PEI, respectively.

Research objectives

The objective of our systematic review was to explore all current evidence regarding the association between CP and heart disease such as CVD and CHF.

Research methods

MEDLINE, Web of Science and Google Scholar were independently searched by two investigators with the aim to identify eligible studies where the connection between CP and CVDs was researched. The primary outcomes were: (1) Incidence of cardiovascular event [acute coronary syndrome (ACS), chronic coronary disease, peripheral arterial lesions] in patients with established CP; and (2) Incidence of PEI in patients with CHF. The primary outcome measure in most studies was the mean difference between control and patient groups.

Research results

Eight studies were eligible for this review. Studies regarding PEI and CHF showed an important incidence of PEI as well as associated malabsorption of nutritional markers (vitamin D, selenium, phosphorus, zinc, folic acid, and prealbumin) in patients with CHF. However, after substitution of pancreatic enzymes, it seems that, at least, loss of appetite was attenuated. On the other side, studies investigating cardiovascular events in patients with CP showed that CP is associated with an increased risk of CVD (a 2.5-fold higher incidence of ACS). Also, CP with concomitant type 3c diabetes had statistically significant higher incidence of carotid atherosclerotic plaques in comparison to patients with diabetes mellitus of other etiologies. When other risk factors for atherosclerosis (hypertension, smoking, and dyslipidemia) were matched, patients with CP had significantly higher incidence of arterial lesions. Moreover, one recent study showed that PEI is significantly associated with the risk of cardiovascular events in patients with CP.

Research conclusions

Chronic pancreatic tissue hypoxic injury driven by prolonged splanchnic hypoperfusion is likely to contribute to malnutrition and cachexia in patients with CHF. On the other hand, CP and PEI seem to be an independent risk factor associated with an increased risk of cardiovascular events.

Research perspectives

Interplay between malnutrition (intake driven) and cachexia (disease driven) can be seen in both cardiac and pancreatic patients, as well as in sarcopenia (muscle wasting) Current evidence implicates possible association between PEI and malnutrition in patients with CHF as well as CP with or without PEI being an independent risk factor for CVD. However, too simplistic explanations should be avoided. Future prospective studies on this topic are necessary, especially using diagnostic methods for PEI other than fecal elastase-1, like the 13C-trygliceride breath test, secretin enhanced magnetic resonance cholangiopancreatography and serum nutritional markers.