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Table of Contents    
Year : 2019  |  Volume : 67  |  Issue : 2  |  Page : 391-392

Cholecysto-cardiac link: The heart of the matter

Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India

Date of Web Publication13-May-2019

Correspondence Address:
Dr. Arun B Taly
Department of Neurology, National Institute of Mental Health and Neurosciences, Bangalore - 560 029, Karnataka
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.258015

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How to cite this article:
Nagappa M, Taly AB. Cholecysto-cardiac link: The heart of the matter. Neurol India 2019;67:391-2

How to cite this URL:
Nagappa M, Taly AB. Cholecysto-cardiac link: The heart of the matter. Neurol India [serial online] 2019 [cited 2020 Jul 2];67:391-2. Available from:

Acute cholecystitis and cardiovascular disorders share a seemingly unlikely, but complex and reciprocal relationship. Cardiovascular disease is a recognised risk factor for developing acute cholecystitis. Gallstone disease increases the risk of cardiovascular disorders including stroke, coronary artery disease and cardiac failure. Acute cholecystitis complicates about 1.2%-2.7% of all strokes. The hazard ratio of developing ischemic and hemorrhagic stroke among patients with gallstone disease is 1.28 and 1.33, respectively.[1] This risk is higher among those undergoing cholecystectomy. Likewise, patients with stroke undergoing neurosurgical procedures have a higher incidence of acute cholecystitis. Sequence symmetry analyses among patients who develop both myocardial infarction and acute cholecystitis during a fixed time period show that the association is causal.[2] In this issue of Neurology India, Kuroi et al., report six patients who developed acute cholecystitis following cerebrovascular events of diverse nature within 2-35 days. They have suggested that the diagnosis may be missed unless suspected, and hypothesise possible mechanisms leading to cholecystitis in this setting.[3] Among patients with stroke, neurological manifestations of altered sensorium, aphasia, dysarthria and motor weakness may overshadow the symptoms and signs of acute cholecystitis leading to a delayed diagnosis.[4]

Acute cholecystitis or inflammation of the gall bladder may be associated with gallstones (calculus cholecystitis) or may occur without any evidence of gallstones (acalculus cholecystitis). While the former is commoner, acalculus cholecystitis is associated with higher mortality rates ranging from 10% to 90%, as compared with 1% in the case of calculus cholecystitis. Acute cholecystitis may accompany or mimic cardiovascular illnesses. Acute cholecystitis may manifest with severe chest pain and dyspnea. Thus, the clinical features of acute cholecystitis may mimic cardiovascular disorders leading to the mistaken diagnosis of angina pectoris, ischemic heart disease, syncope and arrhythmias. Patients may even undergo thrombolysis and other cardiac interventions for this 'pseudo-coronary' syndrome. Electrocardiogram (ECG) may show ST segment elevation or depression and T-wave inversion. Mechanisms of ECG changes in the setting of acute cholecystitis include reduced coronary blood flow due to a distended bile duct, tachycardia, increased blood pressure and increased renin levels, coronary vasospasm mediated by the vagal reflex (the cardio-biliary reflex) and inflammation of other visceral organs. There may even be elevation of markers of acute myocardial injury such as creatine kinase, troponin and heart-type fatty acid binding protein.[5] Increases in heart rate and mean arterial pressure have been observed during surgical manipulation of the gallbladder. This has been attributed to a common sympathetic supply to the heart and gallbladder from the fifth thoracic spinal segment, the so-called 'cholecysto-cardiac' link.[6] This calls for vigilance among the intensivists and other medical personnel while dealing with these subjects.

Cardiovascular disorders may be initially mistaken for acute disorders of the gallbladder. Congestive cardiac failure may manifest with pain in the right upper quadrant of abdomen. Ultrasonographic evidence of an oedematous gallbladder, which is secondary to an increase in portal venous pressure or ischemia caused by cardiac instability, further leads to the mistaken diagnosis of cholecystitis.[7] Some of these changes may be transient and reverse with the improvement of cardiac function and may not warrant surgery for cholecystitis.

Acute cholecystitis complicates a proportion of patients with underlying cardiac disease, particularly aortic dissection and congestive cardiac failure. An intensive care unit stay heightens the risk of developing cholecystitis. Cardiovascular disease increases the risk of developing acute cholecystitis among patients with asymptomatic gall stones.[8] Acute cholecystitis may develop concurrently with the cardiac event or may occur after a varying interval. The increased risk of developing symptomatic gall bladder disease has been shown to persist for years.

The reasons underlying the development of calculus cholecystitis include conversion of asymptomatic to symptomatic gallstones because of drugs used to treat myocardial infarction, hypercholesterolemia, hemodynamic alterations, dietary changes and deliberate weight loss which may promote gallstone formation.[2] The main mechanisms leading to acalculus cholecystitis include ischemia and bile stasis, followed by secondary infection by enteric organisms. Hypovolemic shock, cardiac failure, myocardial ischemia, dehydration, as well as diabetes mellitus, vasculitis, cholesterol emboli, and sepsis contribute to ischemia. On the other hand, fever, dehydration, parenteral nutrition, opioid-induced sphincter of Oddi spasm, gastrointestinal hypomotility, and positive-pressure mechanical ventilation contribute to bile stasis. Ischemia may further be exacerbated by increased intraluminal pressure from bile stasis, which together decrease the gallbladder perfusion pressure. These mechanisms act together and lead to inflammation and necrosis of the gallbladder in the absence of an obstructing gallstone.[9] Having recognised the occurrence of acute cholecystitis in the setting of stroke or myocardial infarction, its management poses a greater therapeutic challenge. While anti-coagulants and anti-platelets for the vascular event predispose to bleeding during surgery, delayed intervention for cholecystitis places the patient at risk of developing complications such as gallbladder necrosis and sepsis.[10] This necessitates customised decision making.

Cholecystitis and cardiovascular disorders share common risk factors such as age, gender, obesity, metabolic syndrome, hyperlipidemia, insulin resistance, diabetes mellitus, hypertension, unhealthy diet, non-alcoholic fatty liver, chronic obstructive pulmonary disease and lack of physical activity. Low plasma levels of insulin-like growth factor-1 (IGF-1) may lead to the development of both gallstones and coronary artery disease.[11] Cholesterol is the main component of gallstones and atherosclerotic plaques, a key factor for several vascular diseases. Thus, the presence of one condition may predispose to the occurrence of the other. Barring an occasional report,[12] there is converging evidence from population and hospital-based studies as well as meta-analysis that even after adjusting for these shared risk factors, the association between cardiovascular disorders and gallstones is significant, indicating the role of other pathogenic processes.[1],[2],[11],[13],[14] Altered gut microbiota play a key role in the development of gallstones; they increase the risk of cardiovascular diseases as well. Likewise, inflammation may have a common pivotal role. Increased oxidative stress alters bile saturation in the gallbladder and leads to the formation of gallstones, and it is also an important factor in lipid peroxidation and endothelial dysfunction underlying cardiovascular disorders.[15]

In summary, what is already known is that there is a higher than chance association of gallbladder disorders, and cardiovascular and cerebrovascular diseases. Both calculus and acalculus cholecystitis can complicate the clinical scenario of an ischemic cardiac event and stroke, as highlighted by Kuroi et al.[3] However, the exact triggering mechanisms and pathobiology underlying the 'cholecysto-cardiac link' remain to be understood.[6],[7]

  References Top

Wei CY, Chung TC, Chen CH, Lin CC, Sung FC, Chung WT, et al. Gallstone disease and the risk of stroke: A nationwide population-based study. J Stroke Cerebrovasc Dis 2014;23:1813-20.  Back to cited text no. 1
Cher DJ. Myocardial infarction and acute cholecystitis: An application of sequence symmetry analysis. Epidemiology 2000;11:446-9.  Back to cited text no. 2
Kuroi Y, Imazato D, Yamazaki K, Kasuya H. Acute cholecystitis in patients with stroke. Neurol India 2019;67:439-41.  Back to cited text no. 3
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Yoo MC, Yoo SD, Chon J, Han YR, Lee SA. Acute cholecystitis as a rare and overlooked complication in stroke patients: A retrospective monocentric study. Medicine (Baltimore) 2019;98:e14492.  Back to cited text no. 4
Ozeki M, Takeda Y, Morita H, Miyamura M, Sohmiya K, Hoshiga M, et al. Acute cholecystitis mimicking or accompanying cardiovascular disease among Japanese patients hospitalized in a cardiology department. BMC Res Notes 2015;8:805.  Back to cited text no. 5
Haleem S, Ansari MM, Khan TZ, Beg MH. Cholecysto-cardiac link. Indian J Med Res 1991;94:47-9.  Back to cited text no. 6
Al Sheria Y, El Shafeib H, Dajanic A, Al Arifia M, Al Aradia F. Fatal reversal of the cholecysto-cardiac link. J Pediatr Surg Case Rep 2018;32:79-81.  Back to cited text no. 7
Cho JY, Han HS, Yoon YS, Ahn KS. Risk factors for acute cholecystitis and a complicated clinical course in patients with symptomatic cholelithiasis. Arch Surg 2010;145:329-33.  Back to cited text no. 8
Desautels CN, Tierney DM, Rossi F, Rosborough TK. An unrecognized etiology of transient gallbladder pain in heart failure diagnosed with internist-performed point-of-care ultrasound. Crit Ultrasound J 2015;7:2.  Back to cited text no. 9
Salameh JR, Franklin ME Jr. Acute cholecystitis and severe ischemic cardiac disease: Is laparoscopy indicated? JSLS 2004;8:61-4.  Back to cited text no. 10
Olaiya MT, Chiou HY, Jeng JS, Lien LM, Hsieh FI. Significantly increased risk of cardiovascular disease among patients with gallstone disease: A population-based cohort study. PLoS One 2013;8:e76448.  Back to cited text no. 11
Kwon CH, Kang JG, Lee HJ, Kim NH, Sung JW, Cheong E, et al. Absence of association between gallstone and coronary artery calcification. Atherosclerosis 2017;258:51-5.  Back to cited text no. 12
Lee YS, Jang SE, Lee BS, Lee SJ, Lee MG, Park JK, et al. Presence of coronary artery disease increases the risk of biliary events in patients with asymptomatic gallstones. J Gastroenterol Hepatol 2013;28:1578-83.  Back to cited text no. 13
Fan LL, Chen BH, Dai ZJ. The relation between gallstone disease and cardiovascular disease. Sci Rep 2017;7:15104.  Back to cited text no. 14
Upala S, Sanguankeo A, Jaruvongvanich V. Gallstone disease and the risk of cardiovascular disease: A systematic review and meta-analysis of observational studies. Scand J Surg 2017;106:21-7.  Back to cited text no. 15


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