Prognostic Value of Cardiovascular Biomarkers in the Population.

Importance: Identification of individuals at high risk for atherosclerotic cardiovascular disease within the population is important to inform primary prevention strategies. Objective: To evaluate the prognostic value of routinely available cardiovascular biomarkers when added to established risk factors. Design, Setting, and Participants: Individual-level analysis including data on cardiovascular biomarkers from 28 general population-based cohorts from 12 countries and 4 continents with assessments by participant age. The median follow-up was 11.8 years. Exposure: Measurement of high-sensitivity cardiac troponin I, high-sensitivity cardiac troponin T, N-terminal pro-B-type natriuretic peptide, B-type natriuretic peptide, or high-sensitivity C-reactive protein. Main Outcomes and Measures: The primary outcome was incident atherosclerotic cardiovascular disease, which included all fatal and nonfatal events. The secondary outcomes were all-cause mortality, heart failure, ischemic stroke, and myocardial infarction. Subdistribution hazard ratios (HRs) for the association of biomarkers and outcomes were calculated after adjustment for established risk factors. The additional predictive value of the biomarkers was assessed using the C statistic and reclassification analyses. Results: The analyses included 164 054 individuals (median age, 53.1 years [IQR, 42.7-62.9 years] and 52.4% were women). There were 17 211 incident atherosclerotic cardiovascular disease events. All biomarkers were significantly associated with incident atherosclerotic cardiovascular disease (subdistribution HR per 1-SD change, 1.13 [95% CI, 1.11-1.16] for high-sensitivity cardiac troponin I; 1.18 [95% CI, 1.12-1.23] for high-sensitivity cardiac troponin T; 1.21 [95% CI, 1.18-1.24] for N-terminal pro-B-type natriuretic peptide; 1.14 [95% CI, 1.08-1.22] for B-type natriuretic peptide; and 1.14 [95% CI, 1.12-1.16] for high-sensitivity C-reactive protein) and all secondary outcomes. The addition of each single biomarker to a model that included established risk factors improved the C statistic. For 10-year incident atherosclerotic cardiovascular disease in younger people (aged <65 years), the combination of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein resulted in a C statistic improvement from 0.812 (95% CI, 0.8021-0.8208) to 0.8194 (95% CI, 0.8089-0.8277). The combination of these biomarkers also improved reclassification compared with the conventional model. Improvements in risk prediction were most pronounced for the secondary outcomes of heart failure and all-cause mortality. The incremental value of biomarkers was greater in people aged 65 years or older vs younger people. Conclusions and Relevance: Cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality. The addition of biomarkers to established risk factors led to only a small improvement in risk prediction metrics for atherosclerotic cardiovascular disease, but was more favorable for heart failure and mortality.

Exploring the association between acute pancreatitis and biliary tract cancer: A large-scale population-based matched cohort study.

BACKGROUND: Biliary tract cancer (BTC) often goes undetected until its advanced stages, resulting in a poor prognosis. Given the anatomical closeness of the gallbladder and bile ducts to the pancreas, the inflammatory processes triggered by acute pancreatitis might increase the risk of BTC. OBJECTIVE: To assess the association between acute pancreatitis and the risk of BTC. METHODS: Using the Swedish Pancreatitis Cohort (SwePan), we compared the BTC risk in patients with a first-time episode of acute pancreatitis during 1990-2018 to a 1:10 matched pancreatitis-free control group. Multivariable Cox regression models, stratified by follow-up duration, were used to calculate hazard ratios (HRs), adjusting for socioeconomic factors, alcohol use, and comorbidities. RESULTS: BTC developed in 0.94% of 85,027 acute pancreatitis patients and in 0.23% of 814,993 controls. The BTC risk notably increased within 3 months of hospital discharge (HR 82.63; 95% CI: 63.07-108.26) and remained elevated beyond 10 years of follow-up (HR 1.82; 95% CI: 1.35-2.47). However, the long-term risk of BTC subtypes did not increase with anatomical proximity to the pancreas, with a null association for gallbladder and extrahepatic tumors. Importantly, patients with acute pancreatitis had a higher occurrence of early-stage BTC within 2 years of hospital discharge than controls (13.0 vs. 3.6%; p-value <0.01). CONCLUSION: Our nationwide study found an elevated BTC risk in acute pancreatitis patients; however, the risk estimates for BTC subtypes were inconsistent, thereby questioning the causality of the association. Importantly, the amplified detection of early-stage BTC within 2 years after a diagnosis of acute pancreatitis underscores the necessity for proactive BTC surveillance in these patients.

Regional and temporal differences in the associations between cardiovascular disease and its classic risk factors: an analysis of 49 cohorts from 11 European countries.

AIMS: The regional and temporal differences in the associations between cardiovascular disease (CVD) and its classic risk factors are unknown. The current study examined these associations in different European regions over a 30-year period. METHODS AND RESULTS: The study sample comprised 553 818 individuals from 49 cohorts in 11 European countries (baseline: 1982-2012) who were followed up for a maximum of 10 years. Risk factors [sex, smoking, diabetes, non-HDL cholesterol, systolic blood pressure (BP), and body mass index (BMI)] and CVD events (coronary heart disease or stroke) were harmonized across cohorts. Risk factor-outcome associations were analysed using multivariable-adjusted Cox regression models, and differences in associations were assessed using meta-regression. The differences in the risk factor-CVD associations between central Europe, northern Europe, southern Europe, and the UK were generally small. Men had a slightly higher hazard ratio (HR) in southern Europe (P = 0.043 for overall difference), and those with diabetes had a slightly lower HR in central Europe (P = 0.022 for overall difference) compared with the other regions. Of the six CVD risk factors, minor HR decreases per decade were observed for non-HDL cholesterol [7% per mmol/L; 95% confidence interval (CI), 3-10%] and systolic BP (4% per 20 mmHg; 95% CI, 1-8%), while a minor HR increase per decade was observed for BMI (7% per 10 kg/m2; 95% CI, 1-13%). CONCLUSION: The results demonstrate that all classic CVD risk factors are still relevant in Europe, irrespective of regional area. Preventive strategies should focus on risk factors with the greatest population attributable risk.

All classic cardiovascular disease (CVD) risk factors are still relevant in Europe, irrespective of regional area. The differences in the associations of CVD risk factors with overt CVD between regions of Europe are generally small. Minor temporal hazard decreases were observed for non-HDL cholesterol and systolic blood pressure, while a minor hazard increase was observed for body mass index.

Dietary habits among snus users: a population-based cross-sectional study.

Background: The dietary habits among snus users are largely unknown and have not been accounted for in observational studies on the health effects of snus use. Aim: To examine whether snus users eat unhealthier than never tobacco users. Methods: A total of 3,397 male participants, examined between 1994 and 2014 in the Northern Sweden Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) study, were included. Snus use and dietary habits were self-reported using questionnaires, from which intakes of different food groups, macronutrients, and a healthy diet score (HDS) were calculated (the latter as a proxy for overall diet quality). The association between snus use and dietary habits was examined by quantile regression models. Results: In the multivariable-adjusted model, current snus users had a lower HDS (median difference: -0.86 [95% confidence interval: -1.32, -0.40]) than never tobacco users. Snus users also consumed fewer weekly servings of fruits and berries (median difference: -1.03 [-1.65, -0.40]), and their estimated percentage of energy intake consisted of less carbohydrates (median difference: -1.43 [-2.12, -0.74]) and of more total fat (median difference: 0.99 [0.30, 1.67]), saturated fat (median difference: 0.67 [0.29, 1.05]), monounsaturated fat (median difference: 0.44 [0.20, 0.68]), trans fat (median difference: 0.03 [0.01, 0.06]), and alcohol (median difference: 0.21 [0.02, 0.40]). Conclusion: We observed that snus users had an unhealthier diet than never tobacco users. Future studies on the association between snus use and health outcomes should, therefore, consider diet as a potential confounder.

Association between snus use and lipid status in Swedish men.

Snus is a common tobacco product in Sweden, but the cardiovascular risk profile for snus users is less known than for cigarette smokers. We examined the association of snus use with lipid status, particularly in comparison to non-tobacco use and cigarette smoking, using data from 5930 men in the Northern Sweden MONICA study. Tobacco use was self-reported in 1986 to 2014 (24.4% used snus) and blood samples were collected at the same time. Harmonized analyses on non-high-density lipoprotein (non-HDL) cholesterol, HDL cholesterol, and triglycerides were conducted in 2016 to 2018. Three hundred eighty-one snus users had also been examined more than once, allowing us to study the effect of discontinued use (achieved by 21.0%). In multivariable linear regression models, snus use was associated with higher HDL cholesterol and triglyceride concentrations compared to non-tobacco use (p values ≤ 0.04), and it was associated with higher HDL cholesterol concentrations and lower triglyceride concentrations compared to cigarette smoking (p values ≤ 0.02). Snus use was not associated with non-HDL cholesterol concentrations, irrespective of the comparison group (p values ≥ 0.07). There was no indication that higher intensity of snus use led to a worse lipid profile, given that high-consumers had higher HDL cholesterol concentrations than low-consumers (p value = 0.02), or that discontinuation of snus use led to a better lipid profile, given that continued users had lower triglyceride concentrations than discontinued users (p value = 0.03). Further studies are needed to confirm or refute our findings.

[Painful left bundle branch block syndrome: an uncommon but treatable chest pain condition]. / Smärtsamt skänkelblocksyndrom.

Painful left bundle branch block syndrome is an uncommon chest pain condition, which is caused by rate-dependent left bundle branch block in the absence of myocardial ischemia. The onset and resolution of the chest pain follows that of the left bundle branch block aberrancy, with an intensity ranging from mild to incapacitating, and it can be treated by pacemaker implantation (preferably with so-called conduction system pacing, since dyssynchronous myocardial contraction is thought to be the culprit). To date, roughly 70 case reports of painful left bundle branch block syndrome have been published in the literature (with none of them originating from Sweden). In this case report, we present ECG findings from repeated exercise tests in a patient who was diagnosed with painful left bundle branch block syndrome and successfully treated by pacemaker implantation.

Antipsychotic drugs and risk of acute pancreatitis: A nationwide case-control study.

INTRODUCTION: Use of antipsychotic drugs, especially second-generation agents, has been suggested to cause acute pancreatitis in multiple case reports; however, such an association has not been corroborated by larger studies. This study examined the association of antipsychotic drugs with risk of acute pancreatitis. METHODS: Nationwide case-control study, based on data from several Swedish registers and including all 52,006 cases of acute pancreatitis diagnosed in Sweden between 2006 and 2019 (with up to 10 controls per case; n = 518,081). Conditional logistic regression models were used to calculate odds ratios (ORs) in current and past users of first-generation and second-generation antipsychotic drugs (dispensed prescription <91 and ≥91 days of the index date, respectively) compared with never users of such drugs. RESULTS: In the crude model, first-generation and second-generation antipsychotic drugs were associated with increased risk of acute pancreatitis, with slightly higher ORs for past use (1.58 [95% confidence interval 1.48-1.69] and 1.39 [1.29-1.49], respectively) than for current use (1.34 [1.21-1.48] and 1.24 [1.15-1.34], respectively). The ORs were largely attenuated in the multivariable model-which included, among others, alcohol abuse and the Charlson comorbidity index-up to the point where only a statistically significant association remained for past use of first-generation agents (OR 1.18 [1.10-1.26]). CONCLUSION: There was no clear association between use of antipsychotic drugs and risk of acute pancreatitis in this very large case-control study, indicating that previous case report data are most likely explained by confounding.

[Dual ventricular response - a rare and underdiagnosed condition?] / En dold kameleont i EKG: dubbelt kammarsvar efter förmaksimpuls.

Dual ventricular response, also called dual atrioventricular [AV] nodal non-re-entrant tachycardia, is a rare arrhythmic condition, characterized by 1:2 anterograde conduction via dual AV-nodal pathways, that is, one P wave is followed by two QRS complexes. The main symptom is palpitations, and it can be treated by catheter ablation. To date, less than 100 cases of dual ventricular response have been published in the scientific literature. In this case report, we present two patients with dual ventricular response (based on ECG findings), both of whom were identified during a 10-year period at a small hospital in Sweden. The case report exemplifies the potential for underdiagnosis of dual ventricular response, due to its tendency to mimic more common arrhythmic conditions, like supraventricular tachycardia and atrial fibrillation.

Epidemiology of hereditary transthyretin amyloidosis in the northernmost region of Sweden: a retrospective cohort study.

INTRODUCTION: Epidemiological data on hereditary transthyretin (ATTRv) amyloidosis from the northernmost region of Sweden (Norrbotten) are sparse. METHODS: We reviewed the medical records of all incident cases of ATTRv amyloidosis in Norrbotten between 2006 and 2018. Official population and mortality statistics were used to estimate incidence rates and standardised mortality ratios (SMRs). RESULTS: Ninety-three patients were diagnosed with ATTRv amyloidosis between 2006 and 2018 (median age, 72.8 years; 68.8% men; 95.7% Val30Met [p.Val50Met] mutation). The incidence rate per 100,000 persons and year increased from 1.50 (95% confidence interval [CI], 0.84-2.47) cases in 2006-2009 to 4.92 (95%CI, 3.46-6.78) cases in 2016-2018. The SMR in the ATTRv amyloidosis cohort was 2.64 times higher than in the general population in 2006-2018 (95%CI, 1.78-3.77). However, there were indications of lower SMRs over time (2006-2012, 2.96 [95%CI, 1.73-4.74]; 2013-2018, 2.32 [95%CI, 1.23-3.96]) and by use of disease-modifying drugs (no, 3.21 [95%CI, 1.87-5.13]; yes, 2.09 [95%CI, 1.08-3.64]). CONCLUSION: The incidence of ATTRv amyloidosis increased 3-fold in Norrbotten between 2006 and 2018, most likely due to a previous underdiagnosis - with suggestions of lowered mortality during later years, possibly due to the introduction of disease-modifying drugs.

Influence of geographical latitude on vitamin D status: cross-sectional results from the BiomarCaRE consortium.

Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25(OH)D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in six European countries using harmonised immunoassay data from 81 084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48·9 %; median age 50·8 years; examination period 1984-2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65·6-63·8°N), Germany (at 48·4°N), Finland (at 65·0-60·2°N), Italy (at 45·6-41·5°N), Scotland (at 58·2-55·1°N) and Spain (at 41·5°N). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as a comparator, the median 25(OH)D concentration was 3·03, 3·28, 5·41, 6·54 and 9·28 ng/ml lower in the German, Finnish, Italian, Scottish and Spanish cohort, respectively (P-value < 0·001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.

Natriuretic Peptides and Risk of Type 2 Diabetes: Results From the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium.

OBJECTIVE: Natriuretic peptide (NP) concentrations are increased in cardiovascular diseases (CVDs) but are associated with a lower diabetes risk. We investigated associations of N-terminal pro-B-type NP (NT-proBNP) and midregional proatrial NP (MR-proANP) with incident type 2 diabetes stratified by the presence of CVD. RESEARCH DESIGN AND METHODS: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) Consortium, we included 45,477 participants with NT-proBNP measurements (1,707 developed type 2 diabetes over 6.5 years of median follow-up; among these, 209 had CVD at baseline) and 11,537 participants with MR-proANP measurements (857 developed type 2 diabetes over 13.8 years of median follow-up; among these, 106 had CVD at baseline). The associations were estimated using multivariable Cox regression models. RESULTS: Both NPs were inversely associated with incident type 2 diabetes (hazard ratios [95% CI] per 1-SD increase of log NP: 0.84 [0.79; 0.89] for NT-proBNP and 0.77 [0.71; 0.83] for MR-proANP). The inverse association between NT-proBNP and type 2 diabetes was significant in individuals without CVD but not in individuals with CVD (0.81 [0.76; 0.86] vs. 1.04 [0.90; 1.19]; P multiplicative interaction = 0.001). There was no significant difference in the association of MR-proANP with type 2 diabetes between individuals without and with CVD (0.75 [0.69; 0.82] vs. 0.81 [0.66; 0.99]; P multiplicative interaction = 0.236). CONCLUSIONS: NT-proBNP and MR-proANP are inversely associated with incident type 2 diabetes. However, the inverse association of NT-proBNP seems to be modified by the presence of CVD. Further investigations are warranted to confirm our findings and to investigate the underlying mechanisms.

Comparison of dietary trends between two counties with and without a cardiovascular prevention programme: a population-based cross-sectional study in northern Sweden.

OBJECTIVE: To compare temporal trends, over a 20-year period, in dietary habits between a county (Västerbotten) with a CVD prevention programme and a county (Norrbotten) without such a programme. DESIGN: Cross-sectional data from the Northern Sweden MONICA study (survey period 1994, 1999, 2004, 2009 and 2014). Dietary habits were assessed by a semi-quantitative FFQ. SETTING: Counties of Norrbotten and Västerbotten, Northern Sweden. PARTICIPANTS: Five thousand four hundred Swedish adults (mean age 56·9 years; 51·2 % women) from Västerbotten (47 %) and Norrbotten (53 %). RESULTS: No differences in temporal trend for estimated percentage of energy intake from total carbohydrates, total fat, total protein and alcohol were observed between the counties (Pfor interaction ≥ 0·33). There were no between-county difference in temporal trends for overall diet quality (assessed by the Healthy Diet Score; Pfor interaction = 0·36). Nor were there any between-county differences for the intake of whole grain products, fruits, vegetables, fish, sweetened beverages or fried potatoes (Pfor interaction ≥ 0·09). Consumption of meat (Pfor interaction = 0·05) increased to a greater extent in Norrbotten from 2009 and onwards, mainly in men (sex-specific analyses, Pfor interaction = 0·04). Men in Västerbotten decreased their intake of sweets to a greater extent than men in Norrbotten (Pfor interaction < 0·01). CONCLUSIONS: Over a 20-year period in northern Sweden, only small differences in dietary habits were observed in favour of a county with a CVD prevention programme compared with a county without such a programme.

Rising incidence of acute pancreatitis in Sweden: National estimates and trends between 1990 and 2013.

BACKGROUND: Recent reports from western countries have indicated an increased incidence and a decreased mortality in acute pancreatitis. However, the incidence assessment has often been hampered by the inclusion of both first-time and recurrent episodes of acute pancreatitis. METHODS: In this retrospective cohort study, all Swedish residents hospitalized with a first-time episode of acute pancreatitis between 1990 and 2013 were identified using national registers. Sex- and age-standardized incidence rates per 100,000 individuals and year were calculated, as were annual percent changes (APC) from joinpoint regression models. RESULTS: Overall, between 1990 and 2013, 66,131 individuals had a first-time episode of acute pancreatitis in Sweden. Comparing the first five years (1990-1994) to the last four years (2010-2013) of the study period, the overall incidence of acute pancreatitis increased from 25.2 (95% confidence interval (CI): 24.1, 26.3) to 38.3 (95% CI: 37.0, 39.5) cases per 100,000 individuals and year. An increase in incidence was observed irrespective of the subtypes of acute pancreatitis as well as the sex and age of the patients. Although the incidence of complicated acute pancreatitis declined in both men and women between 1990 and 2004, it started to increase in both sexes (APC 3.0; 95% CI: 0.5, 5.5 in men; APC 5.4; 95% CI: 2.6, 8.2 in women) from 2005 onwards. CONCLUSION: Based on nationwide data, the incidence of first-time acute pancreatitis has increased in Sweden over a period of 24 years. The incidence of disease-related complications has also been on the rise during the past few years, after declining for more than 15 years before that.

Time trends of vitamin D concentrations in northern Sweden between 1986 and 2014: a population-based cross-sectional study.

PURPOSE: Vitamin D, produced through cutaneous photosynthesis or ingested via foods or supplements, has generated considerable research interest due to its potential health effects. However, epidemiological data on the time trends of vitamin D status are sparse, especially from northern Europe. We examined the time trend of vitamin D concentrations in northern Sweden between 1986 and 2014. METHODS: We used data on 11,129 men and women (aged 25-74 years) from seven population-based surveys (the Northern Sweden MONICA study), recruited between 1986 and 2014. Serum vitamin D (25-hydroxyvitamin D) status was measured using a one-step immunoassay (Abbott Architect). Multivariable linear regression models, adjusted for age, sex, and a number of other variables, were used to estimate the time trend of vitamin D concentrations. RESULTS: The mean value of vitamin D in the entire study population was 19.9 ng/mL [standard deviation (SD) 7.9], with lower values in men (19.4 ng/mL; SD 7.5) than in women (20.5 ng/mL; SD 8.2). Using the survey in 1986 as reference category, the multivariable-adjusted mean difference [95% confidence interval (CI)] in ng/mL was 2.7 (2.2, 3.3) in 1990, 3.2 (2.7, 3.7) in 1994, 1.6 (1.0, 2.1) in 1999, - 2.0 (- 2.5, - 1.4) in 2004, 1.0 (0.4, 1.5) in 2009, and 3.1 (2.5, 3.6) in 2014. CONCLUSION: In this large cross-sectional study, we observed no clear upward or downward trend of vitamin D concentrations in northern Sweden between 1986 and 2014.

Oral metronidazole use and risk of acute pancreatitis: a population-based case-control study.

OBJECTIVE: Oral metronidazole used in combined regimens for Helicobacter pylori eradication has been associated with an increased risk of acute pancreatitis; however, it is less clear whether a similar association exists for single-regimen metronidazole. We, therefore, examined the association of single and combined regimens of oral metronidazole with risk of acute pancreatitis. METHODS: In this population-based case-control study, all individuals in Sweden (aged 40-84 years) hospitalized with acute pancreatitis between January 2006 and December 2008 were identified from a national hospital register (n=5,996). Controls, matched for calendar year, age, and sex, were randomly sampled from a national population register (n=60,681). Data on oral metronidazole and covariates were extracted from national health and prescription registers. Odds ratios (ORs) of acute pancreatitis, according to timing of the latest metronidazole prescription before hospitalization, were estimated using logistic regression models. Confounding by indication was examined by contrasting the main results with the association when amoxicillin was used as exposure. The robustness of results was examined by calculating incidence rate ratios using a self-controlled case series approach. RESULTS: After adjustment for potential confounders, there was a substantially increased risk of acute pancreatitis within 30 days of oral metronidazole exposure, both for single (OR: 4.06; 95% confidence interval [CI]: 1.90-8.64) and combined (OR: 11.80; 95% CI: 6.86-20.28) regimens, compared to nonexposure. In contrast, the adjusted OR was 1.79 (95% CI: 1.25-2.54) for current use of amoxicillin compared to nonexposure. These results were supported by the self-controlled cases series analysis (incidence rate ratio: 3.30; 95% CI: 2.69-4.06, for single and combined regimens of oral metronidazole pooled). There was no strong association between oral metronidazole and acute pancreatitis more than 30 days after exposure. CONCLUSION: There was an increased risk of acute pancreatitis within 30 days of exposure to single and combined regimens of oral metronidazole. While reverse causality and confounding by indication cannot be entirely excluded, they are unlikely to fully explain the association. These results warrant an increased awareness among physicians.

Pancreatic Cancer Following Acute Pancreatitis: A Population-based Matched Cohort Study.

BACKGROUND: Acute pancreatitis is linked to pancreatic cancer, but the direction of this association is not fully elaborated. METHODS: This was a population-based cohort study including all Swedish residents diagnosed with a first-time episode of acute pancreatitis between 1997 and 2013 and corresponding matched pancreatitis-free individuals from the general population. Hazard ratios for the association between acute pancreatitis and pancreatic cancer were estimated using multivariable Cox regression models. RESULTS: Overall, 49,749 individuals with acute pancreatitis and 138,750 matched individuals without acute pancreatitis were followed up for 1,192,134 person-years (median 5.3 years). A total of 769 individuals developed pancreatic cancer, of whom 536 (69.7%) had a history of acute pancreatitis. The risk of pancreatic cancer was substantially increased during the first few years after a diagnosis of acute pancreatitis but declined gradually over time, reaching a level comparable to the pancreatitis-free population after >10 years of follow-up. In those with non-gallstone-related acute pancreatitis, the risk of pancreatic cancer declined to a level comparable to the pancreatitis-free population only when follow-up time was censored for a second episode of acute pancreatitis or a diagnosis of chronic pancreatitis. Increasing number of recurrent episodes of acute pancreatitis was associated with increased risk of pancreatic cancer. CONCLUSION: These findings imply a delay in the diagnosis of pre-existing pancreatic cancer, if clinically presented as acute pancreatitis. Any association between non-gallstone-related acute pancreatitis and pancreatic cancer in the long-term (>10 years) could be mediated through recurrent acute pancreatitis or chronic pancreatitis.

Fruit and vegetable consumption and risk of cholecystectomy: a prospective cohort study of women and men.

PURPOSE: Epidemiologic data on whether consumption of fruit and vegetables (FVs) decreases the risk of gallstone disease are sparse. Therefore, we examined the association between FV consumption and the 14-year risk of symptomatic gallstone disease (defined as occurrence of cholecystectomy) in a large group of middle-aged and elderly persons. METHODS: Data from two population-based cohorts were used, which included 74,554 men and women (born 1914-1952). Participants filled in a food frequency questionnaire in the late fall of 1997 and were followed up for cholecystectomy between 1998 and 2011 via linkage to the Swedish Patient Register. Cox regression models were used to obtain hazard ratios (HRs). RESULTS: During 939,715 person-years of follow-up, 2120 participants underwent a cholecystectomy (1120 women and 1000 men). An inverse association between FV consumption and risk of cholecystectomy was observed in age- and sex-adjusted analyses (P trend = .036) but not in confounder-adjusted analyses (P trend = .43). The multivariable-adjusted HR was 0.95 (95 % CI 0.83-1.08) for the highest compared with the lowest sex-specific quartile of FV consumption. There was no evidence of interactions with age (P = .25) or sex (P = .72) in analyses pooled by sex. However, an age-by-FV consumption interaction was observed in separate analyses of women (P = .010), with decreased HRs of cholecystectomy for ages up to 60 years. CONCLUSIONS: This study supports an inverse association between FV consumption and risk cholecystectomy in women, although the association was restricted to women aged 48-60 years. In contrast, the study does not support an association in men.

Overall diet quality and risk of recurrence and progression of non-gallstone-related acute pancreatitis: a prospective cohort study.

PURPOSE: An incident episode of acute pancreatitis is often followed by recurrent attacks and/or progression to chronic pancreatitis, especially if the etiology is non-gallstone-related. We examined whether overall diet quality influences the natural history of non-gallstone-related acute pancreatitis. METHODS: Three hundred and eighty-six individuals (born 1914-1952) were included in a prospective study, all of whom had an incident diagnosis of non-gallstone-related acute pancreatitis in the Swedish National Patient Register between 1998 and 2013. Participants were already enrolled in two population-based cohorts and had completed a food frequency questionnaire in 1997. Overall diet quality was calculated using a recommended food score (RFS), which was based on 25 food items. Post-diagnosis follow-up was conducted throughout 2014 for recurrence of acute pancreatitis and/or progression to chronic pancreatic disease (including cancer). Hazard ratios were estimated using Cox models. RESULTS: During 1859 person-years of follow-up, 23.3% of the study population (n = 90) developed recurrent or progressive pancreatic disease. An inverse association was observed between the RFS and risk of recurrent and progressive pancreatic disease after adjustment for age and sex (hazard ratio for each 2-unit increase 0.90, 95% confidence interval 0.81-1.01) (P overall association = 0.06). However, the association became weaker and was not statistically significant after adjustment for other potential confounders, including alcohol drinking and cigarette smoking (P overall association = 0.27). CONCLUSIONS: In this prospective study of individuals with non-gallstone-related acute pancreatitis, there was no clear association between overall diet quality and risk of recurrent and progressive pancreatic disease.

Polypharmacy and risk of acute pancreatitis.

PURPOSE: Drug-induced pancreatitis is receiving increased medical and epidemiological attention. However, as no study has examined the role of polypharmacy per se in the development of acute pancreatitis, we examined the association between polypharmacy and risk of acute pancreatitis. METHODS: A nationwide case-control study was conducted between 2006 and 2008 of Swedish people aged 40-84 years. The Swedish Patient Register was used to identify 6161 cases of first-episode acute pancreatitis. The Swedish Register of the Total Population was used to randomly select 61 637 controls from the general population using frequency-based density sampling, matched for age, sex, and calendar year. The Swedish Prescribed Drug Register was used to assess polypharmacy, defined as the number of unique drugs prescribed during the last 6 months before the index date (i.e. the date of acute pancreatitis for cases and a random date for controls). Odds ratios (ORs), with 95% confidence intervals (CIs), of acute pancreatitis were estimated by unconditional logistic regression, adjusted for matching variables and potential confounding factors. RESULTS: The number of prescribed drugs was associated with a dose-dependent increase in the risk of acute pancreatitis. In the multivariable-adjusted model, compared to those without any prescriptions, the OR was 1.69 (95%CI: 1.55-1.86) for persons with 1-2 drugs, 2.40 (2.20-2.62) for 3-5 drugs, 3.17 (2.88-3.48) for 6-9 drugs, and 4.57 (4.12-5.06) for 10 or more drugs. CONCLUSION: This population-based case-control study shows a dose-dependent association between increasing polypharmacy and risk of acute pancreatitis. These findings provide further insights into drug-induced pancreatitis. Copyright © 2016 John Wiley & Sons, Ltd.