Low-Grade Inflammation in the Association between Mild-to-Moderate Hypertriglyceridemia and Risk of Acute Pancreatitis: A Study of More Than 115000 Individuals from the General Population

Abstract

BACKGROUND How mild-to-moderate hypertriglyceridemia (2–10 mmol/L; 177–886 mg/dL) potentially causes acute pancreatitis is unknown; however, cellular studies indicate that inflammation might be a driver of disease progression. We tested the hypotheses that (a) mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and that (b) the association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis depends on low-grade inflammation. METHODS From the Copenhagen General Population Study and the Copenhagen City Heart Study, 117865 men and women 20–100+ years of age with measurements of nonfasting plasma triglycerides at baseline were followed prospectively for development of acute pancreatitis. RESULTS After multivariable adjustment, a 1 mmol/L (89 mg/dL) higher nonfasting triglyceride concentration was associated with 17% (95% CI, 16%–18%, P = 3 × 10−17) higher plasma C-reactive protein (CRP) and a 4.2% (4.0%–4.4%, P = 6 × 10−17) higher blood leukocyte count. Higher concentrations of nonfasting triglycerides were associated almost linearly with higher risk of acute pancreatitis (P for trend = 5 × 10−6), with hazard ratios of 1.5 (95% CI, 0.9–2.5), 2.0 (95% CI, 1.1–3.6), 2.2 (95% CI, 1.0–4.7), 4.2 (95% CI, 1.6–11.5), and 7.7 (95% CI, 3.0–19.8) in individuals with nonfasting triglycerides of 1.00–1.99 mmol/L (89–176 mg/dL; 46% of the population), 2.00–2.99 mmol/L (177–265 mg/dL; 17%), 3.00–3.99 mmol/L (266–353 mg/dL; 6%), 4.00–4.99 mmol/L (354–442 mg/dL; 2%), and ≥5mmol/L(443 mg/dL; 2%), respectively, vs individuals with <1 mmol/L (89 mg/dL; 27%). The association with risk of acute pancreatitis appeared more pronounced in individuals with CRP of ≥1.39 mg/L (P for trend = 0.001) and leukocytes of ≥7 × 109/L (P = 2 × 10−4) than in those with CRP <1.39 mg/L (P = 0.03) and leukocytes <7 × 109/L (P = 0.04); however, there was no formal evidence of statistical interaction (P = 0.38 for CRP and P = 0.41 for leukocytes). CONCLUSIONS Mild-to-moderate hypertriglyceridemia is associated with low-grade inflammation and higher risk of acute pancreatitis. The association between mild-to-moderate hypertriglyceridemia and risk of acute pancreatitis is possibly partly mediated by low-grade inflammation.

Remnant cholesterol and risk of ischemic stroke in 112,512 individuals from the general population

“…It could also be in combination with inflammation in other tissues such as adipose tissue, liver, and pancreas. In a recent study, we found that mild‐to‐moderate hypertriglyceridemia was associated with low‐grade inflammation and higher risk of acute pancreatitis, and that the association between mild‐to‐moderate hypertriglyceridemia and risk of acute pancreatitis possibly was partly mediated by low‐grade inflammation …”

The enigma of soluble LDLR: could inflammation be the key?

“…How it compares to these other markers and in which diseases remains to be determined. Interestingly, plasma sLDLR in our previous study [4], like nonfasting triglyceridemia in the Copenhagen study [23], positively correlates with anthropometric risk factors of chronic inflammation such as gender, age, and body mass index. If shown to be specific and sensitive, sLDLR could serve as a surrogate marker of inflammation in metabolic, immune, and infectious diseases.…”

“…Moreover, there is a positive correlation between circulating levels of WAT-secreted leptin and inflammatory markers, particularly C-reactive protein (CRP), TNFα, and interleukin (IL)-6 [22]. A recent profiling of a cohort of nearly 118,000 subjects of the Copenhagen City Heart Study and the Copenhagen General Population Study in Denmark has demonstrated a correlation between chronic mild to moderate nonfasting hypertriglyceridemia and markers of inflammation, specifically CRP as well as the blood counts of lymphocytes, neutrophils, and monocytes [23].…”

Elevated triglycerides on admission positively correlate with the severity of hypertriglyceridaemic pancreatitis

“…11 The incidence of AP has been shown to increase by the level of baseline HTG. [12][13][14] HTG appears to have a disease course more severe than that of AP with other aetiologies, 15,16 but whether absolute TG levels are associated with the severity of the clinical course of AP remain controversial. Some studies have indicated a relationship between elevated serum TG levels and pancreatitis-associated complications.…”