Pancreas. 2013 Aug;42(6):1011-5.
Cardiovascular disease and risk of acute pancreatitis in a population-based study.
Bexelius TS, Ljung R, Mattsson F, Lagergren J.
Upper Gastrointestinal Research, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden. firstname.lastname@example.org
The low-grade inflammation that characterizes cardiovascular disorders may predispose these patients to the development of acute pancreatitis. Therefore we investigated this connection in a nation-wide case-control study.
A nested population-based case-control study was performed from 2006-2008 in Sweden. Cases had their first episode of acute pancreatitis in the Patient Register. Controls were randomly selected from all Swedish residents (40-84 years old) matched on age, sex and calendar year. Exposure to cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure, and stroke) was identified in the Patient Register. Relative risk of acute pancreatitis was estimated by odds ratios with 95% confidence intervals using logistic regression adjusting for confounders (matching variables, alcohol disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular diseases).
The study included 6161 cases and 61,637 control subjects. Cardiovascular disorders were positively associated with acute pancreatitis (adjusted odds ratio, 1.30; 95% confidence interval, 1.21-1.39).
This population-based study indicates an association between cardiovascular disease and acute pancreatitis. Specifically, ischemic heart disease and hypertension seem to increase the risk of acute pancreatitis. Further research is needed to determine causality.
The etiology of acute pancreatitis is not completely known. Apart from the 2 major types of risk factors – alcohol, and mechanical obstruction such as gallstones, there are still about a 20% proportion of cases with unknown etiology (1, 2). Until the pathogenesis of acute pancreatitis is elucidated, successful preventive pharmacological action is difficult.
There have been many efforts to prevent development of acute pancreatitis, above all in the setting of post-ERCP (endoscopic retrograde cholangio-pancreatography) using hormonal treatment, such as somatostatin or analogues (3); the idea was to inhibit pancreatic secretion and consequently reduce development of pancreatitis. Also, anti-inflammatory treatment with cortisone (4)and NSAID has been tested with insufficient result.
Here, we investigate the hypothesis that low-grade chronic inflammation as seen in cardiovascular disease could act as a trigger of pancreatitis.
Our approach has been to study a large cohort of patients in Sweden using nationwide health data register to obtain a large sample-size combined with reliable data. Regarding the diagnosis acute pancreatitis, a validation study showed high positive predictive value of an ICD-diagnosis of acute pancreatitis (5).
There has been suggested a connection between the metabolic syndrome and pancreatitis (6) and the role of diabetes mellitus as a risk factor has been discussed (7). Also, in a previous report hypertension has been shown to increase the risk for acute pancreatitis(8). Interestingly, already in the 70’s pancreatic calcifications and other signs of inflammation were seen together with arteriosclerosis in an experimental Cushing’s disease model characterized by hyperglycemia, hyperlipidemia and hypertension (9).
We aimed to study the association between all cardiovascular disorder as a whole, and each disease, such as ischemic heart disease, hypertension, stroke and congestive heart failure. We based our study on 61,61 cases and 61,637 controls from 2006-2008 in Sweden, identified through the Patient Register, and current ICD-10 diagnosis of pancreatitis.
We found a link between occurrences of cardiovascular disease in 32% of cases 32% compared to 20% in controls. This translated into an increased odds ratio of 1.30, with 95% confidence interval of 1.21-1.39. acute pancreatitis, taking into account other potential confounding factors. Specifically, hypertension and ischemic heart disease seemed to increase the risk. The individual associations are seen in Table 1.
Table 1. Risk of acute pancreatitis with regard to cardiovascular disorders
1) Diagnosis of any of the following diseases: hypertension, ischemic heart disease, congestive heart failure, or stroke.
*Adjusted for gender, age category, and calendar year. †Adjusted for matching variables, education, alcohol disease, gallstone disease, chronic obstructive pulmonary disease, type 2 diabetes, number of distinct medications, and other cardiovascular disorders
Significance of our work
Our work could contribute with an expanded view on the etiology of acute pancreatitis; arteriosclerosis locally in the pancreas that could increase the likelihood of developing pancreatitis probably in combination with other factors. To reach the goal of prevention modifiable risk factors such as treatment related factors i.e. drugs could be investigated.
Figure 1. Suggested pathway between cardiovascular disease and acute pancreatitis
- Lindkvist B, Appelros S, Manjer J, Borgstrom A. Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase? Clin Gastroenterol Hepatol. 2004;2(9):831-7.
- Sandzen B, Rosenmuller M, Haapamaki MM, Nilsson E, Stenlund HC, Oman M. First attack of acute pancreatitis in Sweden 1988 – 2003: incidence, aetiological classification, procedures and mortality – a register study. BMC Gastroenterol. 2009;9:18.
- Ueki T, Otani K, Kawamoto K, Shimizu A, Fujimura N, Sakaguchi S, et al. Comparison between ulinastatin and gabexate mesylate for the prevention of post-endoscopic retrograde cholangiopancreatography pancreatitis: a prospective, randomized trial. J Gastroenterol. 2007;42(2):161-7.
- Zheng M, Bai J, Yuan B, Lin F, You J, Lu M, et al. Meta-analysis of prophylactic corticosteroid use in post-ERCP pancreatitis. BMC Gastroenterol. 2008;8:6.
- Razavi L, Lindblad. Acute pancreatitis – a validation study in the Swedish Patient Register. Pancreatology. 2011;In press.
- Rajesh G, Kumar H, Menon S, Balakrishnan V. Pancreatitis in the setting of the metabolic syndrome. Indian J Gastroenterol. 2012.
- Girman CJ, Kou TD, Cai B, Alexander CM, O’Neill EA, Williams-Herman DE, et al. Patients with type 2 diabetes mellitus have higher risk for acute pancreatitis compared with those without diabetes. Diabetes Obes Metab. 2010;12(9):766-71.
- Eland IA, Sundstrom A, Velo GP, Andersen M, Sturkenboom MC, Langman MJ, et al. Antihypertensive medication and the risk of acute pancreatitis: the European case-control study on drug-induced acute pancreatitis (EDIP). Scand J Gastroenterol. 2006;41(12):1484-90.
- Wexler BC. Arteriosclerosis of the pancreas and changes in the islets of Langerhans of repeatedly bred rats. Br J Exp Pathol. 1970;51(2):107-13.