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Resistant Atherosclerosis: The Need for Monitoring of Plaque Burden. BACKGROUND AND PURPOSE: Recent studies indicate that patients with lower levels of low-density lipoprotein cholesterol (LDL-C) have greater regression of coronary plaque. In 2002, we found that carotid plaque progression doubled cardiovascular risk. In 2003, we therefore implemented a new approach, treating arteries instead of risk factors. Since then, we have seen many patients with carotid plaque progression despite very low levels of LDL-C, suggesting other causes of atherosclerosis. We studied the relationship of achieved LDL-C and change in LDL-C to progression/regression of atherosclerosis, before and after 2003. METHODS: All 4512 patients in our clinic database with at least 2 measurements of LDL-C and carotid total plaque area approximately a year apart and complete data for analyses (n=2025 before and 2487 after December 31, 2003) were included in the study. RESULTS: Baseline total plaque area was significantly higher after 2003 (129.56±134.32 versus 113.33±121.52 mm2; P<0.0001), and plaque progression was significantly less after 2003 (2.94±37.11 versus 12.62±43.24 mm2; P<0.0001). Many patients with LDL-C <1.8 mm had plaque progression (47.5%), and change in LDL-C was not correlated with plaque progression/regression. Increasing age and serum creatinine contributed to resistant atherosclerosis. CONCLUSIONS: Many patients have Resistant Atherosclerosis, failing to achieve regression of atherosclerosis despite low levels of LDL-C. Instead of relying on LDL-C, measuring plaque burden may be a more useful way of assessing individual response to therapy, particularly in resistant atherosclerosis.