Macrovascular Disease Is Associated With Increased Plasma Apolipoprotein A-IV Levels in NIDDM

Abstract

Apolipoprotein A-IV (apoA-IV) might play an important role in lipoprotein metabolism, including modulation of triglyceride-rich lipoprotein catabolism, reverse cholesterol transport and cholesteryl ester transfer protein (CETP) activity. Increased apoA-IV levels have been reported in plasma from NIDDM patients. The aim of the present study was to look for a possible association between plasma apoA-IV level and prevalence of macrovascular disease in NIDDM. One hundred and thirty-six NIDDM patients were studied (71 men, 65 women). Macrovascular disease was assessed in each patient by a standardized questionnaire, physical examination, resting electrocardiogram (ECG), and laboratory evaluation (ankle/arm blood pressure ratio, continuous wave Doppler velocimetry). Moreover, patients without any history of coronary heart disease and showing a normal resting ECG underwent a bicycle exercise test or a dipyridamole thallium scintigraphy to detect possible silent myocardial ischemia. Among the 136 NIDDM patients, 56 had macrovascular disease. ApoA-IV levels were significantly higher in NIDDM patients with macrovascular disease than in NIDDM patients without macrovascular disease (20.9 +/- 8.6 vs. 13.3 +/- 5.3 mg/dl; P < 0.001). The influence of different factors, such as age, BMI, cigarette smoking, hypertension, total cholesterol, triglycerides, HDL cholesterol, apoA-IV level, apoA-IV phenotype, fasting glycemia, fasting C-peptide, and microalbuminuria, on the prevalence of macrovascular disease was analyzed using a logistic regression model. In the univariate analysis, apoA-IV level (P < 0.00001), age (P = 0.0087), hypertension (P = 0.012), microalbuminuria (P = 0.018), triglycerides (P = 0.02), and fasting C-peptide (P = 0.03) were positively associated with macrovascular disease. In the multivariate analysis, macrovascular disease was positively associated only with apoA-IV (P < 0.0001) and age (P = 0.003) and negatively associated with HDL cholesterol (P = 0.013). These results indicate that increased plasma apoA-IV level is associated with an increased prevalence of macrovascular disease in NIDDM. Moreover, apoA-IV, in NIDDM patients, appears to be a better marker for macrovascular disease than triglycerides.