Metabolic and lifestyle risk factors for acute pancreatitis in Chinese adults: A prospective cohort study of 0.5 million people

Abstract

Background: Little prospective evidence exists about risk factors and prognosis of acute pancreatitis in China. We examined the associations of certain metabolic and lifestyle factors with risk of acute pancreatitis in Chinese adults.

Methods and findings: The prospective China Kadoorie Biobank (CKB) recruited 512,891 adults aged 30 to 79 years from 5 urban and 5 rural areas between 25 June 2004 and 15 July 2008. During 9.2 years of follow-up (to 1 January 2015), 1,079 cases of acute pancreatitis were recorded. Cox regression was used to estimate adjusted hazard ratios (HRs) for acute pancreatitis associated with various metabolic and lifestyle factors among all or male (for smoking and alcohol drinking) participants. Overall, the mean waist circumference (WC) was 82.1 cm (SD 9.8) cm in men and 79.0 cm (SD 9.5) cm in women, 6% had diabetes, and 6% had gallbladder disease at baseline. WC was positively associated with risk of acute pancreatitis, with an adjusted HR of 1.35 (95% CI 1.27-1.43; p < 0.001) per 1-SD-higher WC. Individuals with diabetes or gallbladder disease had HRs of 1.34 (1.07-1.69; p = 0.01) and 2.42 (2.03-2.88; p < 0.001), respectively. Physical activity was inversely associated with risk of acute pancreatitis, with each 4 metabolic equivalent of task (MET) hours per day (MET-h/day) higher physical activity associated with an adjusted HR of 0.95 (0.91-0.99; p = 0.03). Compared with those without any metabolic risk factors (i.e., obesity, diabetes, gallbladder disease, and physical inactivity), the HRs of acute pancreatitis for those with 1, 2, or ≥3 risk factors were 1.61 (1.47-1.76), 2.36 (2.01-2.78), and 3.41 (2.46-4.72), respectively (p < 0.001). Among men, heavy alcohol drinkers (≥420 g/week) had an HR of 1.52 (1.11-2.09; p = 0.04, compared with abstainers), and current regular smokers had an HR of 1.45 (1.28-1.64; p = 0.02, compared with never smokers). Following a diagnosis of acute pancreatitis, there were higher risks of pancreatic cancer (HR = 8.26 [3.42-19.98]; p < 0.001; 13 pancreatic cancer cases) and death (1.53 [1.17-2.01]; p = 0.002; 89 deaths). Other diseases of the pancreas had similar risk factor profiles and prognosis to acute pancreatitis. The main study limitations are ascertainment of pancreatitis using hospital records and residual confounding.

Conclusions: In this relatively lean Chinese population, several modifiable metabolic and lifestyle factors were associated with higher risks of acute pancreatitis, and individuals with acute pancreatitis had higher risks of pancreatic cancer and death.

Fig 1. Adjusted HRs for acute pancreatitis by BMI and WC.

BMI was classified as <20.0, 20.0 to <22.5 (reference), 22.5 to <25.0, 25.0 to <27.0, and ≥27.0 kg/m². WC was classified by quintiles (<71.7, 71.7 to <77.0 [reference], 77.0 to <82.2, 82.2 to <88.5, and ≥88.5 cm). Model was stratified by sex and region and adjusted for age at baseline, education, smoking, alcohol, and medication (aspirin, ACE-I, beta blockers, statins, diuretics, Ca⁺⁺ antagonists, metformin, and insulin). Time since birth was used as the underlying time scale with delayed entry at age at baseline. HRs were plotted against the mean level in each adiposity group. Log-scale was used for the y-axis. The squares represent HRs, and the vertical lines represent 95% CIs. The area of the squares is inversely proportional to the variance of the log HRs. The numbers above the vertical lines are point estimates for HRs, and the numbers below the lines are numbers of events. BMI was missing in 2 participants. SD was 3.4 kg/m² for BMI and 9.8 cm for WC. ACE-I, angiotensin-converting enzyme inhibitor; BMI, body mass index; HR, hazard ratio; WC, waist circumference.

Fig 2. Adjusted HRs for acute pancreatitis by RPG.

RPG levels for participants without previously diagnosed diabetes at baseline were classified as ≤4.4 (reference), 4.5 to <5.6, 5.6 to <7.8, and ≥7.8 mmol/L. RPG was missing in 8,156 participants. Model was stratified by sex and region and adjusted for age at baseline, education, smoking, alcohol, medication (aspirin, ACE-I, beta blockers, statins, diuretics, Ca⁺⁺ antagonists, metformin, and insulin), and fasting time. Time since birth was used as the underlying time scale with delayed entry at age at baseline. HRs were plotted against the mean level in each adiposity group. Log-scale was used for the y-axis. The squares represent HRs, and the vertical lines represent 95% CIs. The area of the squares is inversely proportional to the variance of the log HRs. The numbers above the vertical lines are point estimates for HRs, and the numbers below the lines are numbers of events. There was evidence that the association of acute pancreatitis risk with RPG deviated from linearity (p = 0.001). The adjusted HR per 1 mmol/L higher RPG was 1.04 (1.02–1.07) (p < 0.001). ACE-I, angiotensin-converting enzyme inhibitor; HR, hazard ratio; RPG, random plasma glucose.

Fig 3. Adjusted HRs for acute pancreatitis by total physical activity.

Total physical activity was classified by quintiles (<8.7 [reference], 8.7 to <14.3, 14.3 to <21.9, 21.9 to <33.2, and ≥33.2 MET-h/day). Model was stratified by sex and region and adjusted for age at baseline, education, smoking, alcohol, and medication (aspirin, ACE-I, beta blockers, statins, diuretics, Ca⁺⁺ antagonists, metformin, and insulin). Time since birth was used as the underlying time scale with delayed entry at age at baseline. HRs were plotted against the mean level in each adiposity group. Log-scale was used for the y-axis. The squares represent HRs, and the vertical lines represent 95% CIs. The area of the squares is inversely proportional to the variance of the log HRs. The numbers above the vertical lines are point estimates for HRs, and the numbers below the lines are numbers of events. ACE-I, angiotensin-converting enzyme inhibitor; HR, hazard ratio; MET-h/day, metabolic equivalent of task hours per day.