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CLINICAL RESEARCH: ATHEROSCLEROSIS

The apolipoprotein CI content of triglyceride-rich lipoproteins independently predicts early atherosclerosis in healthy middle-aged men

Anders Hamsten, MD, PhD^_*, Angela Silveira, PhD^_*, Susanna Boquist, MD, PhD, Rong Tang, MD, M. Gene Bond, PhD, Ulf de Faire, MD, PhD and Johan Björkegren, MD, PhD^_*,_*

^* Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden
Cardiology Unit, Karolinska Hospital, Stockholm, Sweden
Division of Ultrasound, Department of Neurobiology and Anatomy, Wake Forest University, Winston-Salem, North Carolina
Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden

Manuscript received October 6, 2004; accepted December 6, 2004.

^_* Reprint requests and correspondence: Dr. Johan Björkegren, Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Karolinska Hospital, 171 76 Stockholm, Sweden (Email: johan.bjorkegren{at}ks.se).

OBJECTIVES: In this study, we examined the apolipoprotein (apo) CI content of triglyceride-rich lipoproteins (TRLs) in relation to established coronary heart disease (CHD) risk factors and early atherosclerosis.

BACKGROUND: In Western society, the postprandial state constitutes a nearly constant stress on the vasculature and the metabolism of lipoproteins. Delayed clearance of postprandial TRL remnants has repeatedly been associated with premature CHD and may include the enrichment of these remnants with apoCI.

METHODS: We examined 72 healthy 50-year-old men with an apoE3/E3 genotype who had undergone an oral fat load test and B-mode ultrasound examination of the intima-media thickness (IMT) of the common carotid artery.

RESULTS: In the fasting state, plasma, very-low-density lipoprotein (VLDL), and low-density lipoprotein cholesterol, proinsulin, and apoB100-containing intermediate density lipoprotein levels were related to IMT (p < 0.05). In the postprandial state, IMT was related to triglycerides at 2 h (p < 0.01), large VLDL concentration at 3 h (p < 0.05), the apoCI plasma and TRL concentrations at 6 h (p < 0.05, p < 0.05), and the apoCI content of TRLs at 6 h (p < 0.002). Multivariate analysis revealed that the apoCI content of TRLs at 6 h (p < 0.0001), plasma triglyceride concentrations at 2 h (p < 0.006), and fasting plasma cholesterol concentration (p < 0.05) independently predicted IMT. In addition, the apoCI content of postprandial TRLs correlated strongly with the cholesterol content (r = 0.64, p < 0.0001).

CONCLUSIONS: Our results indicate that the apoCI content of postprandial TRLs is a novel independent risk factor for early atherosclerosis in normolipidemic healthy middle-aged men with possible implication for the enrichment of TRL remnant lipoproteins with cholesterol.

Abbreviations and Acronyms   apo = apolipoprotein   CHD = coronary heart disease   IMT = intima-media thickness   Sf = Svedberg flotation   TRL(s) = triglyceride-rich lipoprotein(s)   VLDL = very-low-density lipoprotein

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