Atheroma progression in hyporesponders to statin therapy.
OBJECTIVE
Lowering low-density lipoprotein cholesterol (LDL-C) with statins has been demonstrated to slow plaque progression. This antiatherosclerotic effect in patients with minimal LDL-C lowering has not been investigated.


RESULTS
Six hundred forty-seven patients with angiographic coronary artery disease who were commenced on statin therapy underwent serial imaging with intravascular ultrasound. Responders were defined as a percentage reduction in LDL-C of <15%. Disease progression was compared in responders (n=517) and hyporesponders (n=130) to statin therapy. Twenty percentage of patients demonstrated minimal changes in LDL-C, despite commencement of statin therapy. Statin hyporesponders were younger (55 versus 57 years; P=0.01), more likely to be male (79% versus 66%; P=0.005), and obese (body mass index, 31.5 ± 6.1 versus 30.3 ± 5.9 kg/m(2); P=0.04) and less likely to have a history of dyslipidemia (50% versus 66%; P<0.001). Baseline levels of systolic blood pressure (127 ± 15 versus 132 ± 17 mm Hg; P=0.01) and LDL-C (2.5 ± 0.6 versus 3.4 ± 0.8 mmol/L; P<0.001) were lower in statin hyporesponders. Baseline percent atheroma volume was similar between statin hyporesponders and responders (36.9 ± 9.8% versus 38.3 ± 9.2%; P=0.13). On serial evaluation, greater progression of percent atheroma volume (1.19 ± 0.48% versus 0.09 ± 0.43%; P=0.003) was observed in statin hyporesponders. After adjusting for baseline clinical characteristics and measures of plaque burden, statin hyporesponders still exhibited greater atheroma progression (+0.83 ± 0.58% versus -0.21 ± 0.52%; P=0.006).


CONCLUSIONS
A substantial proportion of patients with coronary artery disease fail to achieve effective reductions in LDL-C, despite prescription of statin therapy. Greater progression of atherosclerosis is observed in these patients. Our current study underscores monitoring LDL-C level after the commencement of statin to ensure adequate response to statin therapy.
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Yu
Y
Kataoka
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Julie
J
St John
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Kathy
K
Wolski
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Kiyoko
K
Uno
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Rishi
R
Puri
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
E Murat
EM
Tuzcu
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH.
Steven E
SE
Nissen
From the South Australian Health and Medical Research Institute, Heart Health Theme, University of Adelaide, Adelaide, Australia (Y.K., S.J.N.); and C5 Research (J.S.J., K.W., K.U., R.P., S.E.N.) and Department of Cardiovascular Medicine, Heart and Vascular Institute (R.P., E.M.T., S.E.N.), Cleveland Clinic, OH. stephen.nicholls@sahmri.com.
Stephen J
SJ
Nicholls
D000368:Aged; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D008078:Cholesterol, LDL / Q000097:blood; D002986:Clinical Trials as Topic; D003324:Coronary Artery Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D018450:Disease Progression; D004351:Drug Resistance; D050171:Dyslipidemias / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D015995:Prevalence; D012307:Risk Factors; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D018084:Ultrasonography, Interventional
D015415:Biomarkers; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors
LDL cholesterol; coronary artery disease; disease progression; statins, HMG-CoA