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CLINICAL RESEARCH: LIPIDS AND CORONARY RISK

Clinical Predictors of Plaque Progression Despite Very Low Levels of Low-Density Lipoprotein Cholesterol

Ozgur Bayturan, MD^_*, Samir Kapadia, MD^_*, Stephen J. Nicholls, MBBS, PhD^_*,,,_*, E. Murat Tuzcu, MD^_*, Mingyuan Shao, MS^_*, Kiyoko Uno, MD, PhD^_*, Ajai Shreevatsa, MD^||, Andrea J. Lavoie, MD^_*, Kathy Wolski, MPH^_*, Paul Schoenhagen, MD^_*, and Steven E. Nissen, MD^_*

^_* Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, Ohio
Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio
Imaging Institute, Cleveland Clinic, Cleveland, Ohio
Center for Cardiovascular Diagnostics and Prevention, Cleveland Clinic, Cleveland, Ohio
^|| Department of Internal Medicine, Case Western Reserve University, Cleveland, Ohio

Manuscript received October 23, 2009; revised manuscript received December 10, 2009, accepted January 2, 2010.

^_* Reprint requests and correspondence: Dr. Stephen J. Nicholls, Department of Cardiovascular Medicine, Heart and Vascular Institute, Mail Code JJ-65, Cleveland Clinic, 9500 Euclid Avenue, Cleveland, Ohio 44195 (Email: nichols1{at}ccf.org).

Objectives: The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol (LDL-C).

Background: Despite achieving very low levels of LDL-C, many patients continue to demonstrate disease progression and have clinical events.

Methods: A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials. Patients who achieved an on-treatment LDL-C level of 70 mg/dl (n = 951) were stratified as progressors (n = 200) and nonprogressors (n = 751) and compared.

Results: Despite achieving LDL-C 70 mg/dl, >20% of patients continued to progress. There were no demographic differences between groups. Progressors demonstrated higher baseline levels of glucose (117.1 ± 42.5 mg/dl vs. 112.1 ± 40.0 mg/dl, p = 0.02), triglycerides (157.5 mg/dl vs. 133.0 mg/dl, p = 0.004), and a smaller decrease of apolipoprotein B (–25.1 ± 3.4 mg/dl vs. –27.4 ± 3.35 mg/dl, p = 0.01) at follow-up. Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C 70 mg/dl included baseline percent atheroma volume (p = 0.001), presence of diabetes mellitus (p = 0.02), increase in systolic blood pressure (p = 0.001), less increase in high-density lipoprotein cholesterol (p = 0.01), and a smaller decrease in apolipoprotein B levels (p = 0.001), but not changes in C-reactive protein (p = 0.78) or LDL-C (p = 0.84).

Conclusions: Residual risk factors are associated with the likelihood of disease progression in patients who achieve very low LDL-C levels. In addition, the association between apolipoprotein B and atheroma progression highlights the potential importance of LDL particle concentration in patients with optimal LDL-C control. This finding highlights the need for intensive modification of global risk in patients with coronary artery disease.

Key Words: low low-density lipoprotein • intravascular ultrasound • apolipoprotein B • atherosclerosis

Abbreviations and Acronyms   Apo = apolipoprotein   EEM = external elastic membrane   HDL-C = high-density lipoprotein cholesterol   IVUS = intravascular ultrasound   LDL-C = low-density lipoprotein cholesterol   PAV = percent atheroma volume   TAV = total atheroma volume

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