Long-Term Change in Cholesterol in Relation to Inflammation-Sensitive Plasma Proteins: A Longitudinal Study

Purpose The nature of the relationship between inflammation and elevated serum lipid levels is incompletely understood. This longitudinal study explores whether elevated levels of inflammation-sensitive plasma proteins (ISPs) are a risk factor for developing increased cholesterol and triglyceride levels. Methods Five ISPs (fibrinogen, orosomucoid, α1-antitrypsin, haptoglobin, and ceruloplasmin) were measured in a population-based cohort of nondiabetic healthy men aged 38 to 50 years at baseline. Subjects were reexamined after a mean of 6.2 years. The development of hypercholesterolemia (cholesterol ≥ 6.5 mmol/L [≥251 mg/dL]) and hypertriglyceridemia (triglycerides ≥ 2.3 mmol/L [≥204 mg/dL]) during follow-up was studied in relation to the number of elevated levels of ISPs (i.e., in the top quartile). Results Of men with initially normal cholesterol levels (<6.5 mmol/L; n = 2224), proportions of men with no, one, two, and three or more elevated ISP levels at baseline who developed hypercholesterolemia were 12%, 13%, 16%, and 20%, respectively (p for trend = 0.0002). This relationship remained significant after adjustments for cholesterol level at baseline and other confounding factors. The relationship between ISP levels and future hypertriglyceridemia was attenuated and nonsignificant after adjustments for confounding factors. Conclusion In apparently healthy men with initially normal cholesterol levels, elevated ISP levels are a risk factor for development of hypercholesterolemia.